Ординатура / Офтальмология / Английские материалы / Progress in Lens and Cataract Research_Hockwin_2002
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Table 1. Increase in water proton relaxation in the lens equator as a function of the relative area
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Rabbit |
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Equatorial cortex over lens long axis |
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% |
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Normal |
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18.0 2.4 |
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Galactosemic |
30.4 6.6a |
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Diabetic |
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39.9 7.5b |
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Student’s t tests: a p 0.002; b p 0.00 when compared |
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with normal rabbits. n 6 in each experiment. |
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Table 2. Water diffusion coefficient (D 10 5 cm2 s 1) in the lens cortex |
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Rabbit |
Coordinate |
Aqueous humor |
Anterior |
Posterior |
Equator-1 |
Equator-2 |
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Normal |
X |
2.15 |
0.11 |
0.56 |
0.13 |
0.60 |
0.18 |
0.61 |
0.16 |
0.59 |
0.13 |
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Diabetic |
X |
2.06 |
0.22 |
0.99 |
0.34 |
0.82 |
0.14 |
0.64 |
0.16 |
0.71 |
0.34 |
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Normal |
Y |
2.05 |
0.29 |
0.48 |
0.18a |
0.61 |
0.17b |
0.72 |
0.26 |
0.62 |
0.20 |
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Diabetic |
Y |
2.13 |
0.09 |
0.96 |
0.01a |
1.12 |
0.28b |
0.92 |
0.21 |
1.09 |
0.35 |
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Normal |
Z |
2.04 |
0.09 |
0.66 |
0.13 |
0.64 |
0.18c |
0.55 |
0.13d |
0.59 |
0.13 |
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Diabetic |
Z |
2.22 |
0.07 |
1.00 |
0.21 |
0.99 |
0.04c |
0.83 |
0.10d |
0.82 |
0.08 |
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Normal |
x y |
1.91 |
0.48 |
0.39 |
0.12f |
0.52 |
0.15 |
0.69 |
0.16e |
0.65 |
0.10f |
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Galactosemic |
x y |
2.43 |
0.03 |
0.39 |
0.13 |
0.88 |
0.43 |
0.64 |
0.22 |
0.67 |
0.17 |
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Normal |
y z |
1.77 |
0.33g |
0.37 |
0.14h |
0.49 |
0.16 |
0.57 |
0.17 |
0.57 |
0.07h |
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Galactosemic |
y z |
2.67 |
0.48g |
0.48 |
0.13 |
1.50 |
0.91 |
0.86 |
0.29 |
0.54 |
0.32 |
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Figures representing significant differences are italicized. Significant differences based on Student’s t test: a p 0.009; b p 0.05; c p 0.03; d p 0.04; e p 0.01; f p 0.007; g p 0.012; h p 0.027. n 4–6 in each experiment.
In the normal lens, there appears a resistance to water diffusion which is not only related to fiber orientation but also to intracellular impedance because of the similar D values between anterior/posterior cortex and the equators (table 2). A significant difference was seen only when the gradients were turned on in the secondary coordinates (x y, x z, and y z); in this case, the equatorial water self-diffusion was less restricted than the anterior cortex (table 2). On the other hand, it is also clear that the lens cortex of the diabetic rabbit showed an increase in water diffusion along the y- and z-axes, i.e., along the long axis of lens fibers. This result indicates an increase in the intracellular fluidity.
Water Diffusion in Rabbit Lens |
173 |
Along the x y, x z, and y z axes, there was no significant difference in water diffusion between normal and galactosemic lenses, although the galactosemic aqueous humor showed an increase in water diffusivity (table 2).
Discussion
The change in the behavior of water movement is clearly demonstrated in the sugar cataracts: lengthening of T2 (and by implication, T1) in the deeper regions of the lens equators of both the diabetic and the galactosemic rabbits is evident (table 1). This result also strongly indicates an increase in hydration consistent with the osmotic change in sugar cataracts. It is possible that the stages of cataract progression are not equivalent in the two animal models tested in the present study; indeed, the signal-producing equatorial zone appears to enlarge more in the lens of the diabetic rabbit (table 1). Since the lens equator is normally hidden behind the iris even with maximal mydriasis, it is inaccessible through optical means. MRI therefore remains the only method available for the assessment of cataract progression in this region.
The impedance to water diffusion appears related to lens fiber orientation (table 2) and it may also be related to the presence of subcellular structures especially the well-ordered lens proteins known as the crystallins. In addition, a significant change in the lens of the diabetic rabbits is detected, i.e., an increase in water diffusion along the long axis of the lens fiber (table 2). This result is the hallmark of the subcellular lens change in the diabetic rabbit indicating loss of protein order. Since the diabetic change is induced by activation of the polyol pathway, it remains to be seen if the change can be prevented or reversed with aldose reductase inhibitors.
The increase in the water diffusivity in the aqueous humor of the galactosemic eye suggests an increase in the proportion of free water (or a loss of large aqueous humor components, e.g., albumin) or simply an increasing thermal convection. The galactosemic lens results are slightly different from those from a previous ex vivo study [16] in that, like in the normal lens, water diffusion does not appear to be restricted only to fiber orientation (table 2), although enlarged areas of increasing relaxation times are still seen (table 1). We should point out that the nuclear region remains signal void indicating little of no change in water-proton relaxation. In theory, polyols should also accumulate in the nucleus. It remains to be determined if the nucleus simply does not produce sufficient polyols or is more resistant to water inflow.
In conclusion, we have demonstrated the feasibility of diffusion-weighted MRI in vivo. The results indicate that the subcellular preclinical changes can be detected with MRI.
Cheng |
174 |
Acknowledgments
This project was supported by research grant EY07620 from National Eye Institute, National Institutes of Health, Bethesda, Md. MRI was performed at Massachusetts General Hospital-NMR Center, Charlestown Navy Yard, Charlestown, Mass. The skilled technical assistance of Dr. Hua Xiong and Dr. Yaotang Wu is gratefully acknowledged.
References
1Kärger J, Pfeifer H, Heink W: Principles and application of self-diffusion measurements by nuclear magnetic resonance. Adv Magn Reson 1988;12:1–89.
2Tanner JE: Self diffusion of water in frog muscle. Biophys J 1979;28:107–116.
3Cleveland GC, Chang DC, Hazelwood CF, Rorschach HE: Nucelar magnetic resonance measurement of skeletal muscle. Biophys J 1976;16:1043–1053.
4Van Donkelaar CC, Kretzers LJ, Bovendeerd PH, Lataster LM, Nicolay K, Janssen JD, Drost MR: Diffusion tensor imaging in biomechanical studies of skeletal muscle function. J Anat 1999; 194:79–88.
5Yao L, Sinha U: Imaging the microcirculatory proton fraction of muscle with diffusion-weighted echo-planar imaging. Acad Radiol 2000;7:27–32.
6Turner R, Le Bihan D, Maier J, Vavrek R, Hedges LJ, Pekar K: Echo-planar imaging of intravoxel incoherent motions. Radiology 1990;177:407–414.
7Chien D, Kwong KK, Gress D, Buonanno F, Buxton R, Rosen B: MR diffusion imaging of cerebral infarction in humans. AJNR 1992;13:1097–1102.
8Beauchamp NJ Jr, Ulug AM, Passe TJ, van Zijl PC: MR diffusion imaging in stroke: Review and controversies. Radiographics 1998;18:1269–1283.
9Maier SE, Gudbjartsson H, Patz S, Hsu L, Lovblad KO, Edelman RR, Warach S, Jolesz FA: Line scan diffusion imaging: Characterization in healthy subjects and stroke patients. Am J Roentgenol 1998;171:85–93.
10Clark CA, Werring DJ, Miller DH: Diffusion imaging of the spinal cord in vivo: Estimation of the principal diffusivities and application to multiple sclerosis. Magn Reson Med 2000;43:133–138.
11Werring DJ, Brassat D, Droogan AG, Clark CA, Symms MR, Barker GJ, MacManus DG, Thompson AJ, Miller DH: The pathogenesis of lesions and normal-appearing white matter changes in multiple sclerosis: A serial diffusion MRI study. Brain 2000;123:1667–1676.
12Reese TG, Weisskoff RM, Smith RN, Rosen BR, Dinsmore RE, Wedeen VJ: Imaging myocardial fiber architecture in vivo with magnetic resonance. Magn Reson Med 1996;34:789–796.
13Garrido L, Wedeen VJ, Kwong KK, Spencer UM, Kantor HL: Anisotropy of water diffusion in the myocardium of the rat. Circ Res 1994;74:789–793.
14Cheng HM, Garrido L, Brown E, Aguayo JB: Magnetic resonance microscopy of the kidney; in Pomer S, Hull W (eds): Magnetic Resonance in Nephrourology. Heidelberg, Springer, 1993.
15Beaulieu C, Does MD, Snyder RE, Allen PS: Changes in water diffusion due to Wallerian degeneration in peripheral nerve. Magn Reson Med 1996;36:627–631.
16Cheng HM, Kuan WP, Garrido L, Xiong J, Chang C: High-resolution MR imaging of water diffusion in the rabbit lens. Exp Eye Res 1992;54:127–132.
17Stejskal EO, Tanner JE: Spin diffusion measurements: Spin echos in the presence of a timedependent field gradients. J Chem Phys 1965;42:288–292.
18Cheng HM: Nuclear magnetic resonance studies of ocular tissues. Med Sci Res 1988;15:441–446.
Hong-Ming Cheng, OD, PhD, Schepens Retina Associates, 100 Charles River Plaza, Boston, MA 02114 (USA)
Tel. 1 617 523 7800, Fax 1 617 277 0996, E-Mail hmcheng@nmr.mgh.harvard.edu
Water Diffusion in Rabbit Lens |
175 |
Author Index
Arnarsson, A. 17 |
Kojima, M. 6, 17, 65, 99, 131 |
Sakamoto, A. 99 |
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Ayala, M. 75 |
Kosano, H. 167 |
Sakamoto, Y. 99 |
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Bando, M. 149 |
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Sasaki, H. 17, 65, 99 |
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Löfgren, S. 75 |
Sasaki, K. 17, 65, 99, 131 |
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Cheng, H.-M. 65, 175 |
McCarty, C.A. 25 |
Shui, Y.B. 65 |
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Sliney, D.H. 45 |
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Miyakoshi, M. 131 |
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Dong, X. 75 |
Söderberg, P.G. 75 |
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Mody, V. 75 |
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Duncan, D.D. 81 |
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Muñoz, B. 81 |
Takahashi, N. 65, 131 |
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Dwinger, M. 119 |
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Müller-Breitenkamp, U. 6 |
Takehana, M. 149 |
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Harding, J.J. |
156 |
Nishigori, H. 167 |
Tatami, A. 99 |
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Heinitz, M. |
119 |
Taylor, H.R. 25 |
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Hockwin, O. 1, 6 |
Obazawa, H. 149 |
Vrensen, G.F.J.M. 141 |
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Hook, D.W.A. 156 |
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Ojima, J. 110 |
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Jonasson, F. 17, 65 |
Okuno, T. 110, 131 |
Wegener, A. 6, 119, 141 |
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Jonsson, V. 17 |
Ono, M. 17, 36, 65 |
West, S.K. 81 |
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Kakar, M. 75 |
Saito, H. 110 |
Willekens, B. 141 |
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Katoh, N. 17, 65 |
Sakai, M. 99 |
Yamada, Y. 141 |
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176
Subject Index
ActiveDrive, see Sunglasses
Age-related macular degeneration, effect of visible light 76, 77
Aging
ascorbate free radicals 144
cataract prevalence effects 13–15, 17 climate effects on cataract formation,
see Climate
Alcohol consumption, cataract risk factor 16, 18
Aldose reductase, temperature effects on expression 132
Animal models
accommodative capacity of lenses 7 bovine 143, 152
chickens 7, 162–167 eye pigmentation effects
conditions of lens properties 6, 7 lens fiber morphology in albino and
pigmented rats 135–141 guinea pigs 7, 143
pigeons 7
rabbits 5, 6, 43, 44, 143, 151, 169–174 rodents 6, 43, 71, 113–118, 125–133,
135–140, 143 species differences 5, 6
Ascorbate free radical reductase function in eye 143, 144 isoelectric focusing 144, 145 isoforms 145, 147, 148 purification 146
sizes 146, 147
two-dimensional gel electrophoresis 145, 146
Blue-light hazard effective radiance
arc lamps 110
arc welding 109–111 solar 109
photoretinitis risks 104, 105 sources 105, 107, 108 spectroradiometry 105, 106, 108
Calcium, cataract formation role 139–141 Caloric restriction, cataract prevention 136 Cataract
epidemiology, see Blue-light hazard, Climate, Risk factors, Ultraviolet radiation, Visible light
history of research 2–8 surgery 8
Chaperone, see -Crystallin Climate
epidemiological studies of cataract overview 60, 61, 126 prevalence of lens opacities
age effects 62, 63, 65, 67 cortical cataract 62–64, 66 gender effects 62, 63, 65, 67 mixed cataract 62–64 nuclear cataract 62–64, 66
subcapsular cataract 62–64, 66 study design 61, 62
temperature effects 67, 68 Finland 111
geographical correction factor 79 Iceland 12, 60, 126
Japan 60, 126
177
Climate (continued) Punjab 43
Singapore 60, 126, 131 Thailand 131
Tibet 56
tropical and subtropical 60–68 Contrast sensitivity function
measurement 97 no filter group 97
Tri-Blocker® filter 97, 100 Cornea
edema 117 temperature
measurement 44, 45 variation 43
Corticosteroids, see Steroid-induced cataract
-Crystallin chaperone activity
aging effects 151 assays 152, 153
modification by fructose 6-phosphate and prednisolone-21-hemisuccinate, effects on thermal aggregation alcohol dehydrogenase 154 catalase 155, 158
L-crystallin 153, 154, 157, 158 glyceraldehyde 3-phosphate dehydro-
genase 154, 155 overview 150, 151 tryptophan fluorescence 153,
155–158
glycation sites and features 151, 152, 157 homology with other crystallins 150, 151
Diabetes cataract
history of study 4, 5
risk factor with raised sugar and glucocorticoid levels 150
temperature effects 132
lens water diffusion effects in rabbit 173, 174
protein glycation and chaperone activity 151
temperature effects in rat cataract model 132
Diaphorase, ascorbate free radical reductase activity 145
Dietary deficiency, see Vitamin E, Zinc Droplet keratopathy, pathogenesis 41, 55,
114
Fructose 6-phosphate, effect on -crystallin chaperone activity 152–158
Galactosemia, lens water diffusion effects in rabbit 173, 174
Glare protection, see Sunglasses Glucocorticoid, see Steroid-induced
cataract
Glucose breakdown, effect of nutritional deficiencies and ultraviolet light 115
Glutathione, loss in steroid-induced cataract 162, 167
Heat cataract, see Temperature
Lens
homogenization for studies 3 metabolism 7, 8
water diffusion in rabbit lens diabetes effects 173, 174 diffusion coefficients 171–173 galactosemia effects 173, 174 magnetic resonance imaging
169–171, 174 Lens epithelial cell
albino and pigmented rats 140 fiber differentiation 135 guinea pigs and rats 135
Lens fiber
ball-and-socket 135, 136, 138–140 interdigiting edge protrusions 135–137 morphology in albino and pigmented rats
scanning electron microscopy 136–139 transmission electron microscopy 140
Magnetic resonance imaging, water diffusion in lens 169–171, 174 Maximum tolerable dose, ultraviolet
radiation definition 73
dose-response curve 72, 74
Subject Index |
178 |
rat exposure 71 rationale 71 sensitivity 72–74 study design 71–73
Nuclear cataract
climate effects, see Climate geographical variation 41, 42, 60, 61
Ocular ambient exposure ratio, visible light 77–80, 85, 86, 88, 90, 91
Ocular exposure factor, derivation for ultraviolet light 54
Outdoor exposure, cataract risk factor 16, 17
Phospholipids, binding free calcium on fibrous membranes 141
Photokeratitis, pathogenesis 129, 132 Photoretinitis
blue-light hazards 104, 105 clinical features 104
Prednisolone-21-hemisuccinate, effect on-crystallin chaperone activity 152–158
Pterygium, pathogenesis 41, 52, 53, 55, 114
Rat
lens fiber morphology in albino and pigmented rats 135–141
lens weight changes with aging 3 life expectancy 3
maximum tolerable dose of ultraviolet radiation 71–74
nutritional deficiency interactions with ultraviolet radiation in cataract formation 115–122
temperature and ultraviolet effects in cataract model 126–133
Retinal pigment epithelium, visible light effects 77
Reykjavik Eye Study
cataract risk factor findings 14–18 purpose 12, 13
study design 13, 14
Risk factors, see also Aging, Blue-light hazard, Ultraviolet radiation, Visible light alcohol consumption 16, 18
cortical steroid use 18 outdoors exposure 16 smoking 15
systemic diseases 15
Scanning electron microscopy, lens fiber morphology 136–139
Scheimpflug photography
contrast sensitivity function correlation to lens transparency 97
density data collection 122
effects of nutritional deficiencies 118 geometrical development of various
cataracts 56
lens opacities in various climates 60 Reykjavik Eye Study 14
Senile cataract
follows same trend as presbyopia 133 pathogenesis 4, 126
Smoking, cataract risk factor 15–17 Steroid-induced cataract
chick embryo lens culture studies culture system 163, 164 glucocorticoid effects on turbidity
163–166
sex steroid effects on turbidity 163–166
corticosteroids as cataract risk factor 18
glutathione loss in lens 162, 167 Schiff base formation 162
Sunglasses
glare protection study
ActiveDrive features 95, 100, 101 contrast sensitivity function
group without filters 97 measurement 97 Tri-Blocker® filter 97, 100
phototopic conditions 100–102 scotopic conditions 101, 102 subjects 96
Tri-Blocker® filter features 94, 95, 101
transmittance 94 ultraviolet protection 50, 57
Superoxide dismutase, effect of nutritional deficiencies and ultraviolet light 113
Subject Index |
179 |
Temperature, see also Climate corneal temperature
measurement 44, 45 variation 43
-crystallin chaperone activity, glycation effects on thermal aggregation of substrates
alcohol dehydrogenase 154 catalase 155, 158
L-crystallin 153, 154, 157, 158 glyceraldehyde 3-phosphate 154, 155
environmental 54, 55, 67, 68, 125–133 industrial 44, 45
lens variation 43
rat cataract model effects of ambient temperature
aldose reductase expression 132 body weight differences 127 control 129
diabetic cataract subgroup 127, 128, 132
study design 126, 127, 130–132 ultraviolet-B exposure subgroup 129,
132
Transmission electron microscopy, lens fiber morphology 140
Tri-Blocker® filter, see Sunglasses Tryptophan fluorescence, -crystallin
modification studies 153, 155, 156, 158
Ultraviolet radiation, see also Climate, Maximum tolerable dose, ultraviolet radiation
absorption 47
action spectra 46, 47, 70 animal cataract induction 23, 43 biological plausibility of cataract
association 22, 23, 41, 42 Chesapeake Bay Waterman’s Study 52 classification 22, 114
daily exposure estimation 33, 34 environmental differences 53, 54 epidemiological evidence linking to
cataracts
chronological review of sunlight studies 25–27
consistency 28
exposure estimation for studies 36–38 limitations of studies 41
odds ratio 24
prospects for study 29, 30, 56, 57 specificity of association 28, 29 strength, temporal sequence and dose-
response 23, 24, 28 exposure algorithms 52 field of view studies
exposure algorithms 52, 53
ocular exposure dose characterization 51, 52
study design 48–50
geometrical gradients in temperature distribution and absorbed ultraviolet 40–57
ground level exposure factors 33 lid opening 49, 50
lifetime exposure 49 luminance 49, 50
mannequin exposure studies 32–39, 48 minimizaton of exposure 29 nutritional deficiency interactions in
cataract formation, see Vitamin E, Zinc
ocular exposure factor 54 protective measures 35 radiance 51
reflectance 48 scattering 46, 47, 126
sunglasses protection 50, 57
Ultraviolet Monitoring Network in Japan 38, 39
Visible light, see also Blue-light hazard age-related macular degeneration role
76, 77
exposure modeling
advantages and limitations of model 85–87
cumulative exposure per day 77 education effects 84
ethnicity differences 76, 82 gender differences 76, 77, 82
geographic correction factor 78, 87, 88 milli-visible Maryland sun years 78,
80, 81
Subject Index |
180 |
ocular-ambient exposure ratio 77–80, 85, 86, 88, 90, 91
photophobia 84
statistical variations of model parameters 88–91
Vitamin E
deficiency and ultraviolet radiation interactions in cataract formation capsulo-endothelial layer effects 118,
119
rat body weight 117, 119, 120 Scheimpflug photography 118, 122 slitlamp microscopy 117, 120, 122 study design 115, 116
functions in eye 115
Water diffusion, see Lens
Zinc
deficiency and ultraviolet radiation interactions in cataract formation capsulo-endothelial layer effects 118,
119
rat body weight 117, 119, 120 Scheimpflug photography 118, 122 slitlamp microscopy 117, 120, 122 study design 115, 116
eye distribution 114, 115 functions 115
lens growth role 122
Subject Index |
181 |