Index

A

A3 adenosine receptors (A3ARs) adenosine triggered activation, 27 aqueous humor dynamics, 25 ATP, 28–29

IOP regulation, 29–30

macroscopic current characteristics, 28 pseudo exfoliation syndrome, 26

2 adrenergic agonists, 439 Acetazolamide, carbonic anhydrase

inhibitor, 247–248 Activin A gene regulation, 359

Activity base protein profile (ABPP), 329 Adenosine receptor agonists and

antagonists, 447–449 Adrenergic agonists, 249–252 Angiopoietin like factor 7, 343–344 Apolipoprotein D (APOD), 341–342

Apraclonidine, adrenergic agonists, 250–251 Aquaporin (AQP) water channels, 6 Aqueous blood flow and ciliary blood flow

adrenergic 2 agonists, 291–293 in anesthetized rabbits, 289 hypothetical curves, 290–291 partial pressure of oxygen (PO2)

change, 293–295 Aqueous humor (AH)

EPMA production

Naþ, Kþ activated ATPase, 107–108 NPE and PE cells swelling, 116 thermodynamic force, 116–117 unidirectional secretion, pathways

for, 114–115 osmolarity, 88

outflow increasing agents, 439–440 outflow resistance pathway

regions, 432–433 corneoscleral meshwork, 165

juxtacanalicular connective tissue (JCT), 166–167

primary open angle glaucoma (POAG), 171

Schlemm’s canal, 167–170 trabecular meshwork, 166

production suppressing agents, 437–439 secretion, 162

unconventional pathway, 162–163 Aqueous humor dynamics

cAMP dependent protein kinase A, 55–56 clinical syndromes

diabetes mellitus, 242 exfoliation syndrome, 241–242 Fuchs’ uveitis syndrome, 243

glaucomatocyclitic crisis, 243–246 myotonic dystrophy, 246

normal tension glaucoma, 240 ocular hypertension, 237–238

pigment dispersion syndrome, 240–241 primary open angle glaucoma, 238–240

drugs aVecting

adrenergic agonists, 249–252

carbonic anhydrase inhibitors, 246–248 cholinergic agonists, 253–254 prostaglandin analogues, 252–253

experimental drugs cytochalasins, 257 dopaminergic agonists and

antagonists, 254–255 latrunculins, 257–258 AT1 receptor antagonists, 255–256 rho kinase inhibitors, 258 serotonin agonists, 258–259

formation process and production, 55 inflow fuction, 57

normal values, human aqueous flow, 233–234

episcleral venous pressure, 234–235 outflow facility, 234

uveoscleral outflow, 235–237 retinal pigment epithelium cells, 58–60 trabecular meshwork cells, 58

472

Aqueous humor dynamics (cont.) water movement rates, epithelial

barriers, 54

Aqueous humor dynamics, animal models cats

aqueous flow rate, 207–208 drug eVects, 220

episcleral venous pressure, 216 fluorophotometry, 208, 212–213 IOP normal values, 195, 200 outflow facility, 209 tonography, 211

uveoscleral outflow, 215 dogs

canine glaucoma, 220–221 episcleral venous pressure, 216 fluorophotometry, 208, 212–213 force displacement method, 217 IOP normal values, 195, 201–202 outflow facility, 209

uveoscleral outflow, 215 mouse

aqueous flow rate, 207–208 confocal microscopy, 208–209 episcleral venous pressure, 216 fluorophotometry, 208 glaucoma and IOP, 218–219 intracameral microneedle

method, 217–218

IOP normal values, 195–196 outflow facility, 209 uveoscleral outflow, 215

nonhuman primates aqueous flow rates, 207 direct cannulation, 217

episcleral venous pressure, 216 fluorophotometry, 208, 212–213 glaucoma model, 221

IOP normal values, 195, 203–204 outflow facility, 209–210 tonography, 211

uveoscleral outflow, 215 rabbits

aqueous flow rate, 207–208 episcleral venous pressure, 216 fluorophotometry, 212–213

IOP normal values, 195, 197–199 ocular hypertension, 219–220 outflow facility, 209

telemetry, 206

Index

tonography, 211

uveoscleral outflow, 214–215 rats

aqueous flow rate, 207–208 glaucoma model, 219

IOP normal values, 195–196 outflow facility, 209 tonometry, 205

Aqueous humor dynamics, components and measurements

aqueous humor flow

confocal microscopy, 208–209 direct sampling method, 209 fluorophotometry, 208 formation, 206–207

rate of flow, 207–208 episcleral venous pressure

intracameral microneedle method, 217–218 normal values, 196–202

venomanometer, 217 intraocular pressure, 195

normal values, 196–204 telemetry, 206

tonometry and manometry, 205 outflow resistance

fluorophotometry, 212–213 perfusion technique, 213 tonography, 211–212

trabecular outflow pathway, 209–210 uveoscleral outflow

intracameral tracer methods, 216 mathematical calculation, 215–216 pathways, 213–215

Aqueous humor inflow–outflow link hypothesis, CE

chloride channels and transporters, 125 gap junctions, 129

in glaucoma, 124 glutamatergic system

glutamate transporters, 144 mGluR1 receptor, 142–143 neurotransmission, 141–142

L arginine nitric oxide (NO) signalling, 140–141

neuroendocrine signaling

circadian rhythms entrainment, 145–148 immune circuitry, 148–150

neuropeptides and peptide hormones galanin, 131

gene expression and secretion, 127–128 Naþ/Hþexchanger (NHE)

inhibition, 133–136 natriuretic peptides, 132–133 neurotensin, 129–130

and processing enzymes, 128–129 proteolytic processing, 129–130 secretory factors, 126–127

signal regulation, neprilysin, 136–138 somatostatin (SST), 130–131 synthesis, 126

physiological functions, 124 Aqueous humor outflow resistance

fluorophotometry, 212–213 perfusion technique, 213 tonography, 211–212

trabecular outflow pathway, 209–210 Aqueous humor secretion

ciliary epithelium fundamental basis of, 30–31 structure of, 6–7

circulation, 32 formation mode, 4–5 function of, 2–3

inflow and outflow pathways, 3–4 potential unidirectional reabsorption

ciliary epithelium, 18 iris root, 19

regulation, 33

A3 adenosine receptors, 25–30 carbonic anhydrase, 25–27

Cl channels swelling activation, 20–22 cyclic adenosine monophosphate, 23–25 net ciliary epithelial secretion, 19–20

species variation, 31–32 topography, 32 unidirectional secretion

centrality of NaCl secretion, 8 NaCl extrusion, NPE cells, 12–17 PE–NPE gap junctions, NaCl

passage, 10–12

solute and water secretion, 6, 8 stromal NaCl uptake, 9–10 transcellular and paracellular

components, 8–9 water transfer, stroma, 17

Arteriovenous pressure gradient, 274 Asparagine–proline–alanine (NPA), 49 Astrocytes, ganglion cell injury, 309 AT1 receptor antagonists, 256

B

adrenergic antagonists, 248–249adrenergic receptors, 23–24 Basement membrane

aqueous outflow pathway, 177 hydraulic conductivity (Lp) and

morphological structure, 177B crystallin, 351–352

blockers, 438

Bimatoprost, prostaglandin analogues, 244, 252

2 microglubulin, 342 Bone morphogenic proteins

(BMPs), 390–391, 454

Brimonidine, adrenergic agonists, 250–251 Bumetanide inhibitor, 106, 112, 116–117

C

Calpain II, 395

Carbonic anhydrase inhibitors, 25–27, 246–248, 438–439

Cell–cell adhesion protein, 52 Cellular chloride, EPMA

chemical potential driving force, 106 eVects of CO2/HCO3 , 104 Naþ Kþ–2Cl cotransporter, 104–106

Ceruloplasmin gene regulation, 360–361 Chitinase3, 357–358

Cholinergic agonists, 253–254 Chronic neurodegenerative diseases

glutamate role, 311–312

nitric oxide (NO) role, 310–311 purines role

basic model, 312

neuroprotection by adenosine, 314–315 pressure and ATP release, 313

P2X7 and NMDA receptors, 313–314 Ciliary blood flow, aqueous production

adrenergic 2 agonists, 291–293 in anesthetized rabbits, 289 ciliary body, 283–284

fluorophotometer measurement, 285–288 hypothetical curves, 290–291

LDF measurement, 284

partial pressure of oxygen (PO2) change, 293–295

pseudofacility study, 282–283

Ciliary blood flow, aqueous production (cont.)

sampling depth, 284–285

topical brimonidine eVects, 291–292 Ciliary body secretory epithelium

anatomy, 72 animal models

Cx32 and Cx26 in, 92–93 Cx43 protein, 92

aqueous humor (AH) production, 72–73 gap junction channels

conductance and structural properties, 89–90

connexins, 73–79 role of, 73

model predictions, 87–89 parameters derivation

definition, 80

diVusion and convection, 84–85 hydrostatic and osmotic gradients,

83–84

isotonic transport, 79–80 normalized values, 84 osmolarity, 80–83 perturbation analysis, 82 water flow and solute flux, 80

parameters evaluation, 85–87 PE and NPE cell layers, 71–72 water permeability, 91

Ciliary epithelium basic strategy

NaCl secretion centrality, 8 solute and water secretion, 6, 8 transcellular and paracellular

components, 8–9 and EPMA

energy spectra, 101

intracellular elements K and P, 101–103 PE and NPE cells, 102

fundamental basis, 30–31

potential transcellular reabsorption, transport components, 18

structure of, 6–7

transport components, transcellular secretion

NaCl extrusion, NPE cells–aqueous humor, 12–17

PE–NPE gap junctions, NaCl passage, 10–12

stromal NaCl uptake, 9–10

water transfer, stroma–aqueous humor, 17

Cl channels swelling activation bilateral hypotonicity eVects, 21 regulatory volume decrease (RVD), 22

Clinical syndromes, aqueous humor dynamics diabetes mellitus, 242

exfoliation syndrome, 241–242 Fuchs’ uveitis syndrome, 243 glaucomatocyclitic crisis, 243, 246 myotonic dystrophy, 246

normal tension glaucoma, 240 ocular hypertension, 237–238

pigment dispersion syndrome, 240–241 primary open angle glaucoma, 238–240

Clonidine, adrenergic agonists, 250 Cochlin and IOP lowering, 456–457 Confocal microscopy, aqueous humor

flow, 208–209

Connective tissue growth factor (CTGF), 386, 453

immunoreactivity, 391–392 Western and Northern blot analysis, 389–390

Connexins

Cx43 expression, 76

single channel conductance conductivity/permeability

properties, 78–79 open probability, 77

voltage dependence and open probability, 75–76

Cribriform region. See Juxtacanalicular connective tissue (JCT)

Cross linked actin networks (CLANs), 435–436

Cyclic adenosine monophosphate (cAMP), 23–25

cationic channel function, 61 and cyclic guanosine

monophosphate, 62–63 protein kinase A, 56–57

Cyclic guanosine monophosphate (cGMP) and cyclic adenosine

monophosphate, 62–64

ion channel activity, AQP1, 60–61 Cyclic nucleotide gated cation channels, 64 Cyclooxygenase inhibitors, 251

Cystic fibrosis transmembrane conductance regulator (CFTR) channels, 62

Cytochalasins cytoskeletal drugs, 257 IOP lowering, 442

Cytoskeletal drugs, glaucoma, 256 cytochalasins, 257

latrunculins, 257–258 rho kinase inhibitors, 258

D

Dexamethasone

altered genes in, 352–354 functions, 352

gene expression by, 355–356 Diabetes mellitus, aqueous humor

dynamics, 242 Dopamine

aqueous flow–blood flow relationship, 292–293

receptors, 13–14 Dorzolamide

aqueous blood flow, 291–292 carbonic anhydrase inhibitor, 247–248

E

E50K mutation, optineurin, 405, 408, 412 Electron probe X ray microanalysis (EPMA)

aqueous humor (AH) production NPE and PE cells swelling, 116 thermodynamic force, 116–117 unidirectional secretion, pathways

for, 114–115 in ciliary epithelium

energy spectra, 101

intracellular elements K and P, 101–103 PE and NPE cells, 102

technique, 99–100 theory, 99

timolol eVect, 117–118 topography

changes in Naþ, Kþ, and Cl , 111 Naþ, Kþ activated ATPase,

inhibition, 107, 111 Naþ Kþ–2Cl cotransporter

inhibition, 112 ouabain eVects, 111, 113

in posterior epithelial cells, 113–114

rabbit iris ciliary body (ICB), 110 total inflow

cellular chloride, 104–106 consensus model, 108–109 feasibility, 103

gap junctions, PE and NPE cells, 104 Naþ, Kþ activated ATPase, 107–108

Elongation factor 1 , 339–340 Endothelin 1, 13–14. See also Human

glaucoma

Epinephrine, cyclooxygenase inhibitor, 249–250

Episcleral venomanometry, 217

Episcleral venous pressure (EVP), 234–235 intracameral microneedle method, 217–218 and intraocular pressure, 295–296

normal values, 196–202 venomanometer, 217

EPMA. See Electron probe X ray microanalysis

Ethacrynic acid inhibitors, 443–444 Exfoliation syndrome, aqueous humor

dynamics, 241–242 Extracellular matrix (ECM)

hydrolysis activators

activator protein 1 (AP 1) pathway, 446 glycosaminoglycans (GAGs), 446–447 matrix metalloproteinases

(MMPs), 445–446 turnover, POAG

BMP 7, 390–391 CTGF, 390 TGF 1, 383–385

F

Fluorophotometry aqueous humor flow, 208

outflow resistance, 212–213 FM2 fluorophotometer, 285–288

Fuchs heterochromic iridocyclitis, aqueous humor dynamics, 243

Functional genomics GeneChip/microarray system, 326–327 protein modifications, 328–329 proteomics and protein arrays, 328 trabecular meshwork, direct sequencing

angiopoietin like factor 7, 343–344 apolipoprotein D (APOD), 341–342

476

Functional genomics (cont.)2 microglubulin, 342 elongation factor , 339–340

functional genomic studies, 335–337 human intact tissue libraries, 337–339 matrix Gla protein (MGP), 340 myocilin, 343

translationally controlled tumor protein (TCTP), 342

G

Galanin, 131

Gap junction channels conductance and structural

properties, 89–90 connexins

in ciliary body epithelium, 74–75 Cx43 expression, 76

double layered epithelium, schematic of, 75

genome of, 74

single channel conductance and permeability, 77–79

voltage dependence and open probability, 75–76

fluid transport, animal models Cx32 and Cx26 in, 92–93 Cx43 protein, 92

NaCl passage cAMP, 12 connexons, 10–11

role of, 73

GeneChip/microarray system, 326–327 Glaucoma. See also Intraocular pressure

(IOP); Primary open angle glaucoma (POAG)

adenosine receptor agonists and antagonists, 447–449

altered outflow, 185 aqueous humor dynamics

adrenergic agonists, 249–252 canine model, 220–221

carbonic anhydrase inhibitors, 246–248 cholinergic agonists, 253–254 diagnosis, 211

experimental drugs, 257–258 mouse model, 218

nonhuman primate model, 221

Index

normal tension glaucoma, 240 outflow facility, 210

primary open angle glaucoma, 238–240 prostaglandin analogues, 252–253

rat model, 219

aqueous outflow pathways trabecular pathway, 432–433 uveoscleral pathway, 433

and aqueous production2 adrenergic agonists, 439blockers, 438

carbonic anhydrase (CA) inhibitors, 438–439

cholinergics, 439

epinephrine and prostaglandin analogs, 440

CD44, 456 cochlin, 456–457

cytoskeleton disrupting agents cytochalasins and latrunculins, 442 protein kinase inhibitors, 444 ROCK inhibitors, 444–445 swinholide A and ethacrynic

acid, 442–444 definition, 324

ECM hydrolysis activators

activator protein 1 (AP 1) pathway, 446 glycosaminoglycans (GAGs), 446–447 matrix metalloproteinases

(MMPs), 445–446

E50K mutation, 405–406, 408–409 functional genomics

GeneChip/microarray system, 326–327 protein modifications, 328–329 proteomics and protein arrays, 328

glaucomatous insults

B crystallin and myocilin, 351–352 chaperone/protein folding, 349–351 dexamethasone role, 352–356 intraocular pressure (IOP), 348–349 osteogenesis related genes, 349

growth factors

bone morphogenic proteins (BMPs), 454 connective tissue growth factor

(CTGF), 453

in IOP regulation, 455 transforming growth factor beta

(TGF ), 451–453

Wnt signaling pathway, 454–455 in human, 361–363

hyaluronan and GAGs, 176 interleukin 1 (IL 1), 455–456 intraocular pressure (IOP), 162 juxtacanalicular tissue (JCT), 433, 436 low outflow resistance, 165 microarray studies

ciliary body, 330

lamina cribrosa, 333–335

retinal ganglion cells (RGC), 332–333 trabecular meshwork, 330–332

myocilin mutation, 165, 398, 400, 403–405 ocular hypertension, 430–431

outflow rates measurement 125I albumin and tonograph

monitors, 434

two level constant pressure perfusion technique, 433–434

primary open angle glaucoma (POAG) ceruloplasmin, 360–361

ECM role, 434–435 ELAM1, 360

gycogen study, 358–359 myocilin gene (MYOC), 436 surgical therapy, 440–441

Schlemm’s canal and POAG, 170–171 serotonergic agonists, 449–451

serum amyloid A2 (SAA2), 457 therapies for, 436–438 trabecular meshwork (TM), 432,

435–436, 446 unconventional pathway, 163 viral vectors, 458

WD repeat domain 36, 412 Glaucomatocyclitic crisis, aqueous humor

dynamics, 243–246 Glaucomatous damage, ganglion cells

cell death mechanisms

lamina cribrosa distention, 307–308 neurochemical imbalances, 309–315 vascular compromise, 308–309

cell injury, 302

chronic dysfunction and secondary death, 306–307

elevated IOP, 304–306 parasol cell damage, 303–304

Glutamate, chronic neurodegenerative diseases, 311–312

Glycogen, diVrential gene regulation chemokine (C Cmotif ) ligand 2

(CCL2), 359

mimecan and activin A, 359 Glycosaminoglycans (GAGs), 446–447

proteoglycans role, 175 testicular hyaluronidase role, 176

Goldmann equation, 194–195 IOP regulation, 432

Grant’s equation, 211

H

Heptanol, EPMA, 104, 111, 113 Homomeric subunits, AQP

central pore, 50

channel classification, 48–49 tetrameric organization and

transmembrane topology, 49 Human glaucoma

endothelin 1 role, 361 gene regulation, 363 trabecular meshwork, 362

Hydraulic conductivity, 174, 177

I

Ibopamine, 255 Immunohistochemistry

bB1 crystallin YOC transgenic mice, 398, 401

myocilin, 401

optineurin, 406–407, 409–410 TSP 1, 386–388

Interleukin 1 (IL 1) and IOP lowering, 455–456 Intraocular pressure (IOP)

adenosine receptor agonists and antagonists, 447–449

aqueous humor

A3AR antagonists, 25–30adrenergic receptors, 23–24 carbonic anhydrase inhibition, 25–27 function, 2

inflow and outflow rate, 3–4 production and trabecular outflow, 195

cats and dogs, 220 components, 193–194 cytokines, 455–457

cytoskeleton disrupting agents, 441–445 ECM hydrolysis activators, 445–447

Intraocular pressure (IOP) (cont.) episcleral venous pressure, 164, 295–296 fluctuation, 431–432

ganglion cells, 304–306 glaucoma, 162

Goldmann equation, 194–195 growth factors, 451–455 manometry and tonometry, 205 mice, 218

nonhuman primates, 221

normal values in human, 197–204 ocular blood flow and eVects

arteriovenous pressure, 274–275 choroidal regulation, 278–279 pressure–volume relationship, 279–281 volume of blood, 275–277

pharmacological regulation mechanism, 438

rats, 219 regulation, 432

Schlemm’s canal, 167–168 serotonergic agonists, 449–451 telemetry, 206

Ion channel interactions cAMP and cGMP, 62–63 fluid movement, 61–62 NPE and RPE cells, 62 ocular epithelia, 64 physiological role, 61 water permeation, 60–61

Iris ciliary body (ICB), 100–101, 110

J

Juxtacanalicular connective tissue (JCT), 172 extracellular matrix, 172–173

hydraulic conductivity (K), 174–175 quick freeze/deepetch (QFDE) method, 175 Schlemm’s canal role, 166–167

L

Lamina cribrosa (LC) cells, 333–335 Laser Doppler flowmetry (LDF), ciliary

blood flow

anterior and posterior measurement site, 285

measurement, 284 sampling depth, 284–285

Laser trabeculoplasty (LTP), 171 Latanoprost, prostaglandin analogues,

244, 252, 254

Latrunculins and IOP lowering, 442 Local osmotic gradients, 6, 8

M

Manometry, IOP measurement, 205 Matrix Gla protein (MGP), 340, 384

Matrix metalloproteinases (MMPs), 445–446 Midget cells (P cells), 303

Mimecan upregulation, TGF 2, 359 Mitogen activated protein kinase

(MAPK), 411 MYOC gene, 391, 393 Myocilin

glaucomatous insults, 351–352 primary open angle glaucoma (POAG), 165, 343, 345

function, 395–396 immunohistochemistry, 401

light and electron microscopy, 400, 402–404

Northern blot analysis, 397 role in outflow resistance, 396 secretory mechanism, 394–395 structure, 393–394

Western blot analysis, 398–399 Myotonic dystrophy, aqueous humor

dynamics, 246

N

NaCl extrusion, NPE cells–aqueous humor Cl channels

ClC 3, 15 pICln, 16

rate limiting factor, 14 Kþ channels

functions, 16 rectifiers, 17

Naþ, Kþ activated ATPase ATP–ADP hydrolysis, 12 cAMP activated kinase, 13 endothelin 1 and nitric oxide

synthase, 14

NPE and PE cells, 12–13 protein kinase C, 13–14

NaCl secretion, 8

Naþ, Kþ activated ATPase, 107–109 Naþ Kþ–2Cl cotransporters

(symports), 9–10

Neuroendocrine, AqH inflow–outflow link hypothesis

circadian rhythms, peripheral clocks advantages, 148

clock gene expression, 147 cortisol and melatonin, 145

immune circuitry, 148–150 signal regulation, neprilysin

inflow and outflow AqH, 140 inhibitory eVects, 139–140

negative feedback mechanism, 138–139 trabecular meshwork (TM) cells

markers and peptide receptors expression, 138

neuropeptide receptor activation, 136–137

secretogranin II (SgII), 136 Neuropeptides, AqH inflow–outflow link

hypothesis galanin, 131

gene expression and secretion, 127–128 Naþ/Hþexchanger (NHE)

activation and inhibition, 135–136 AqH secretion, 135

NHE isoforms, 134 natriuretic peptides, 132–133 neurotensin, 129–130

and processing enzymes, 128–129 proteolytic processing, 129–130 secretory factors, 126–127

signal regulation, neprilysin, 136–138 somatostatin (SST), 130–131 synthesis, 126

Nitric oxide (NO), chronic neurodegenerative diseases, 310–311

Nonpigmented ciliary epithelial cells A3 adenosine receptors, 25–30 NaCl extrusion, aqueous humor

Cl channels, 14–16 Kþ channels, 16–17

Naþ, Kþ activated ATPase, 12–14 and pigmented ciliary epithelial cells

ciliary epithelial secretion, 30–31

Cl channels swelling activation, 20–22 cyclic adenosine monophosphate, 23–25 NaCl passage, gap junctions, 10–12

potential transcellular reabsorption, 18 stromal NaCl uptake, 9–10

Nonpigmented epithelium (NPE) apical–apical interface, 89 aquaporin distribution, 54 blood–AH barrier, 73

Cx26 and Cx31, 74–75 Cx40 and Cx43, 74 fluid transport, 88, 92 membranes of, 81–82 osmolarity, 83

Normal tension glaucoma, aqueous humor dynamics, 240

Northern blot analysis, 389, 397

O

Ocular aquaporins (AQPs) aqueous humor dynamics

cAMP dependent protein kinase A, 55–56

circulation, 48

formation process and production, 55 inflow function, 57

retinal pigment epithelium cells, 58–60 trabecular meshwork cells, 58

water movement rates, epithelial barriers, 54

characteristics, 47–48 distribution

aquaporin homologues expression, 50–51 crystalline lens, 50

lens maintenance, 52 role of AQP1, 53

water movements regulation, 52–53 homomeric subunits

central pore, 50

channel classification, 48–49 tetrameric organization and

transmembrane topology, 49 ion channel interactions

cAMP and cGMP, 62–63 cystic fibrosis transmembrane

conductance regulator, 62 fluid movement, 61–62

NPE and RPE cells, 62 ocular epithelia, 64 physiological role, 61 water permeation, 60–61

Ocular aquaporins (AQPs) (cont.) physiology and pathophysiology, 64 therapeutic development, 65

Ocular blood flow, intraocular pressure eVects arteriovenous pressure, 274–275

choroidal regulation, 278–279 pressure–volume relationship, 279–281 volume of blood, 275–277

Ocular ciliary epithelium (CE), AqH dynamics

chloride channels and transporters, 125 gap junctions, 129

in glaucoma, 124 glutamatergic system

glutamate transporters, 144 mGluR1 receptor, 142–143 neurotransmission, 141–142

L arginine nitric oxide (NO) signalling, 140–141

neuroendocrine signaling

circadian rhythms entrainment, 145–148 immune circuitry, 148–150

neuropeptides and peptide hormones galanin, 131

gene expression and secretion, 127–128 Naþ/Hþexchanger (NHE)

inhibition, 133–136 natriuretic peptides, 132–133 neurotensin, 129–130

and processing enzymes, 128–129 proteolytic processing, 129–130 secretory factors, 126–127

signal regulation, neprilysin, 136–138 somatostatin (SST), 130–131 synthesis, 126

physiological functions, 124

Ocular hypertension, 237–238, 430–431. See also Intraocular pressure (IOP)

Ocular rigidity, 234 Olfactomedin, POAG, 393–394 Open angle glaucoma, 26 Optic nerve head (ONH), 325 Optineurin, POAG

E50K mutation, 405, 408, 412 functional role, 408–409

immunohistochemistry, 406–407, 409–410 TUNEL labeling, 410–411

OPTN gene, 405–406, 409

Ouabain eVects, EPMA topography aqueous humor formation, 117

on epithelial cells, 113

Naþ, Kþ activated ATPase, 107–108, 111 Outflow facility, aqueous humor dynamics

definition, 209 glaucoma, 210 measurement

fluorophotometry, 212–213 perfusion technique, 213 tonography, 211–212

Outflow resistance pathway definition, 164

regions

corneoscleral meshwork, 165 juxtacanalicular connective tissue

(JCT), 166–167

primary open angle glaucoma (POAG), 171

Schlemm’s canal, 167–170 trabecular meshwork, 166

P

Parasol cells (M cells), 303 Peptidyl glycine amidating monoxigenase

(PAM), 129

Peroxisomal targeting signal (PTS1), 403, 436

Pigment dispersion syndrome, aqueous humor dynamics, 240–241

Pigmented ciliary epithelial cells

and nonpigmented ciliary epithelial (NPE) cells

ciliary epithelial secretion, 30–31

Cl channels swelling activation, 20–22 cyclic adenosine monophosphate, 23–25 NaCl passage, gap junctions, 10–12 potential transcellular reabsorption, 18 stromal NaCl uptake, 9–10

Pigmented epithelium (PE) apical–apical interface, 89 Cx40 and Cx43, 74–75 fluid transport, 88, 92 membranes, 81–82 osmolarity, 83

Pilocarpine, cholinergic agonists, 253–254

Pilocarpus sp., 253

Plasma membrane estrogen receptor, 28 Plasminogen activator inhibitor

(PAI)–1, 391

Posner–Schlossman syndrome. See Glaucomatocyclitic crisis

Potential unidirectional reabsorption, aqueous humor

ciliary epithelium, 18 iris root, 19

Primary open angle glaucoma (POAG), 433 aqueous humor, 171

bone morphogenetic protein 7, 390–391 connective tissue growth factor,

386, 390 ECM role, 434–435 gene expression

ceruloplasmin, 360–361 ELAM1, 360

gycogen study, 358–359 immunohistochemistry, 387–388,

398, 407, 410 myocilin, 343, 345, 393–405

Northern blot analysis, 389, 397 optineurin, 405–412 pathogenetic molecules, 382 surgical therapy, 440–441

and TGF 2, 356 thrombospondin 1, 385–386

transforming growth factor , 382–385 TUNEL labeling, lens apoptosis,

410–411

WD repeat domain 36, 412–413 Western blot analysis, 389, 399–400

Primary open angle glaucoma, aqueous humor dynamics, 238–240

Prostaglandin analogues, 244–245, 252–253, 440

Prostaglandin F2 , 252–253 Protein kinase A (PKA)

cyclic adenosine monophosphate, 55–56

cyclic guanosine monophosphate, 63 Protein kinase C (PKC), 13–15 Protein kinase G (PKG), 63

Protein kinase inhibitors, 444 Proteoglycans, 175 Proteomics, 328

Pseudo exfoliation syndrome, 26

Purines, chronic neurodegenerative diseases basic model, 312

neuroprotection by adenosine, 314–315 pressure and ATP release, 313

P2X7 and NMDA receptors, 313–314

R

Reactive oxygen species (ROS) ATPase activity, 13

ion channel activity, 2

Red blood cells (RBC) flux, 284–285 Retinal ganglion cells (RGC), 381

cell death mechanisms

lamina cribrosa distention, 307–308 neurochemical imbalances, 309–315 vascular compromise, 308–309

cell injury, 302 glaucomatous damage

chronic dysfunction and secondary death, 306–307

elevated IOP, 304–306 ganglion cell types, 303–304

microarray studies, 332–333 optineurin expression, 406

TNF mediated cell death, 408–409 Retinal pigment epithelium (RPE) cells

aquaporins, 53–54

cyclic nucleotide gated cation channels, 64 diVerentiated fetal human

monolayer, 59–60 nonpigmented epithelium cells, 62 solute transportation, 59

Rho associated coiled coil forming kinase (ROCK) inhibitor, 444–445

Rho kinase inhibitors, cytoskeletal drugs, 258

S

Schiotz tonometer, 211 Schlemm’s canal

basement membrane, 177–178 endothelial cell lining, 178–180 giant vacuoles in, 180 glaucomatous eye, 181–182 muscarinic agents, 166

outflow resistance pathway, 171–172 paracellular flow

interendothelial junctions, 183–184 junctional simplification, 184–185 tight junctions in, 182–183

Secreted frizzled related protein 1 (sFRP1), 454–455

Secretogranin II (SgII), AqH oligonucleotide primers, 139

Secretogranin II (SgII), AqH (cont.) PE and NPE communication, 129 in trabecular meshwork cells, 136

Serotonergic agonists, 449–451 Serotonin agonists, 258–259

Serum amyloid A2 (SAA2) gene, 457 Somatostatin (SST)

circadian rhythms entrainment, 145 distribution and functions, 130 immunosuppressive property, 148–149 neprilysin regulation, 140 oligonucleotide primers, 139

pro SST processing, 130–131 Starling resistors, 274

Stromal NaCl

Naþ Kþ–2Cl cotransporters, 9–10 parallel Naþ/Hþ and Cl /HCO3

countertransporters, 10 Superior colliculus (SC), 303

T

Telemetry, IOP measurement, 206 Testicular hyaluronidase, 176 Thrombospondin 1 (TSP 1), 385–386 Tight junctions, Schlemm’s canal. See

Zonulae occludentes Timolol

adrenergic antagonist, 248–249, 251–252 eVect in EPMA, 117–118

Tissue inhibitors of metalloproteinases (TIMPs), 445–446

Tonography, 211–212

Tonometry, IOP measurement, 205 Trabecular meshwork (TM) cells

aquaporin distribution, 50 conventional outflow pathway, 53–54 conventional outflow tract, 57–58 dexamethasone role

altered genes, 352–354 functions, 352

gene expression, 355–356

direct sequencing and mass spectrometry angiopoietin like factor 7, 343–344 apolipoprotein D (APOD), 341–3422 microglubulin, 342

elongation factor , 339–340 functional genomics studies, 335–337 human intact tissue libraries, 337–339

matrix Gla protein (MGP), 340 myocilin, 343

translationally controlled tumor protein (TCTP), 342

and glaucoma

aqueous outflow pathway, 434–436 cytokines, 455–457 cytoskeleton disrupting agents, 441–445 growth factors, 451–455

MMP expression, 446 glaucomatous insults

B crystallin and myocilin, 351–352 chaperone/protein folding, 349–351 dexamethasone role, 352–356 intraocular pressure (IOP), 348–349 osteogenesis related genes, 349

human glaucoma, 361–363 microarray studies, 330–332 outflow pathway

BMP 7, 390–391

CTGF expression, 386, 390 myocilin, 396

optineurin expression, 406–407 TGF , 382–385

TSP 1 expression, 386–388

primary open glaucoma (POAG) gene expression, 358–361

proteome and protein modifications cochlin and myocilin role, 345 functional categories, 347–348 intracellular soluble proteins, 344–345 TGF growth factors study, 346

transforming growth factor 2 (TGF 2) chitinase3, 357–358

definition, 356

osteoblast specific factor (OSF2) role, 357

Trabecular meshwork (TM) cells, AqH outflow

glutamatergic system glutamine synthase and

glutaminase, 144 mGluR1b receptor, 142–143

neprilysin, 138, 140 neuroendocrine phenotype

characteristics of, 136–137 oligonucleotide primers, 136, 139

neuroendocrine signaling

cGMP production and glutamate, 141 NO formation, 140–141

pro inflammatory and immunosuppressive factors, 149–150

Trabecular outflow pathway, 209–210, 432–433

Transcriptome, 326

Transforming growth factor 2 (TGF 2)B crystallin, 351

chitinase3, 357–358 definition, 356

in glaucoma, 325

mimecan and activin A role, 359 osteoblast specific factor (OSF2) role, 357

Transgenic mice, B1 crystallin MYOC immunohistochemistry, 398, 401

light and electron microscopy, 400, 402–404 Western blot analysis, 398–399

Translationally controlled tumor protein (TCTP), 342

Travoprost, prostaglandin analogues, 245, 252

Tumor necrosis factor (TNF ), 406 TUNEL labeling, 410–411

U

Unconventional pathway, aqueous humor, 162–163

Unoprostone, prostaglandin analogues, 245, 252

Uveitis, aqueous humor dynamics, 243

Uveoscleral outflow, aqueous humor dynamics, 235–237

aqueous outflow, 433 intracameral tracer methods, 216 mathematical calculation, 215–216 pathways, 213–215

V

Vascular damage, glaucoma, 308–309

W

WDR36 gene, 412–413

Western blot analysis, 389, 399–400 Wnt signaling pathway, 454–455

Z

Zonulae occludentes, 182–183