- •An Organ of Exquisite Perfection
- •Optical Path
- •Retinal Photoreception
- •Photoreception Optics
- •Photoreception Biochemistry
- •Membrane Voltages
- •Blind Spot
- •Retinal Pathways
- •Through Pathway
- •Receptive Fields
- •Lateral Pathway
- •Retinal Ganglion Cells
- •Retinal Glia
- •References
- •Development of the Foveal Specialization
- •Introduction
- •Foveal Development
- •Specification of Foveal Location
- •Formation of a Rod-Free Zone
- •Cones, Ganglion Cells, and Initial Pit Formation
- •Deep Foveal Pit Formation
- •Foveal Hypoplasia
- •Conclusions and Perspectives
- •Acknowledgments
- •References
- •An Update on the Regulation of Rod Photoreceptor Development
- •Introduction
- •Brief Overview of Retinal Development and Early Stages of Rod Photoreceptor Differentiation
- •Transcription Factors
- •Basic Helix-Loop-Helix Genes
- •Nuclear Receptors
- •Retinoic Acid/Retinoic Acid Receptors
- •Wnt/Frizzled Pathway
- •Taurine
- •Ciliary Neurotrophic Factor/Leukemia Inhibitory Factor/Pleiotrophin/Signal Transducer and Activators of Transcription 3/SOCS
- •Conclusions and Future Prospects
- •References
- •Introduction
- •Retinal Adhesion
- •Physiology of Retinal Adhesion
- •Molecular Mechanisms of Retinal Adhesion
- •Significance of Retinal Adhesion for Retinal Function
- •Photoreceptor Outer Segment Renewal
- •Physiology of Outer Segment Disk Assembly and Disk Shedding
- •Physiology of RPE Engulfment of Shed Outer Segment Fragments
- •Molecular Mechanisms of Shedding and RPE Phagocytosis
- •Significance of Photoreceptor Outer Segment Renewal for Retinal Function
- •Perspective
- •Acknowledgments
- •References
- •Molecular Biology of IRBP and Its Role in the Visual Cycle
- •Introduction
- •IRBP Protein Studies
- •IRBP Null Mice
- •IRBP Induces Experimental Autoimmune Uveitis
- •IRBP Expression During Development
- •Variability in IRBP Expression
- •Molecular Biology of IRBP
- •IRBP Genomic Cloning
- •Evolution of IRBP
- •Identification of DNA cis-Acting Controlling Elements: In Vitro and In Vivo Experiments
- •Transcription Factors and their Role in the Control of IRBP Expression
- •Rx/rax Transcription Factor
- •NrL Transcription Factor
- •Crx Transcription Factor
- •OTX2 Transcription Factor
- •Transgenic Mice
- •Repressors of IRBP Gene Expression
- •Summary and Conjecture
- •Acknowledgments
- •References
- •Regulation of Photoresponses by Phosphorylation
- •Introduction
- •Cone-Specific Kinase, GRK7
- •Protein Kinase C
- •Cyclin-Dependent Kinase
- •Tyrosine Kinases
- •Protein Phosphatases
- •Conclusion
- •References
- •The cGMP Signaling Pathway in Retinal Photoreceptors and the Central Role of Photoreceptor Phosphodiesterase (PDE6)
- •Regulation of Intracellular cGMP Levels in Photoreceptor Cells
- •Downstream Targets of cGMP Action in Photoreceptor Cells
- •cGMP-Dependent Protein Kinase
- •Cyclic Nucleotide-Gated Ion Channels
- •PDE6 Is a High-Affinity cGMP-Binding Protein
- •Compartmentation of cGMP Signaling in Photoreceptor Outer Segments
- •Physiology of the Photoreceptor Response to Light
- •Biochemical Cascade of Visual Excitation
- •Central Components of the cGMP Signaling Pathway
- •Termination and Adaptation of the Light Response
- •Deactivation of Rhodopsin
- •Deactivation of Transducin
- •Deactivation of PDE6
- •Activation of GC
- •Regulation of the CNG Ion Channel
- •Photoreceptor PDE (PDE6) Structure and Function
- •The Cyclic Nucleotide Phosphodiesterase Superfamily
- •Subunit Composition of Rod and Cone PDE6 Holoenzyme
- •Catalytic Subunit
- •Regulatory GAF Domain
- •Catalytic Domain
- •C-Terminal Prenylation
- •PDE6 Has Evolved to Meet the Special Demands of the Central Effector of Visual Transduction
- •PDE6 Regulation
- •Transducin Activation of Rod PDE6 During Visual Excitation
- •Functions of the Regulatory cGMP-Binding GAF Domains of PDE6
- •Potential PDE6 Regulatory Binding Proteins
- •Glutamic Acid-Rich Protein 2
- •Conclusions
- •Acknowledgments
- •References
- •Rhodopsin Structure, Function, and Involvement in Retinitis Pigmentosa
- •Introduction
- •Historical Perspective
- •Rhodopsin, Localization, and Signaling
- •Dark State and Activation
- •Structural Analysis
- •Electron Cryomicroscopy and Crystal Structure
- •Nuclear Magnetic Resonance
- •Cysteine Mutagenesis and Electron Paramagnetic Resonance
- •Other Approaches
- •Retinitis Pigmentosa
- •Transmembrane RP Rhodopsin Mutants
- •Cytoplasmic RP Rhodopsin Mutants
- •Intradiskal RP Rhodopsin Mutants
- •Implications of Receptor Misfolding
- •Nongenetic Contributions to RP
- •Conclusion
- •References
- •Multiple Signaling Pathways Govern Calcium Homeostasis in Photoreceptor Inner Segments
- •Introduction
- •Overview of Ca2+ Regulation in the Inner Segment
- •Voltage-Operated Calcium Channels Play a Central Role in Inner Segment Calcium Regulation
- •Ca2+ Channels in Rods and Cones
- •Photoreceptor Malfunction and Degeneration
- •Therapeutic Strategies
- •Development
- •Acknowledgments
- •References
- •The Transduction Channels of Rod and Cone Photoreceptors
- •The Role of CNG Channels in Photoreceptor Physiology
- •The Activation Phase of the Light Response
- •Recovery After a Light Stimulus and Adaptation to Continuous Illumination
- •CNG Channels in the Synaptic Transmission of Cone Photoreceptors
- •The Molecular Composition of CNG Channels
- •The Basic Activation Properties of CNG Channels
- •Transmembrane Topology and Functional Domains
- •The Cyclic-Nucleotide-Binding Domain
- •The Amino Terminal Domain and Modulation by Calmodulin
- •The P Region
- •The GARP Domain of CNGB1
- •Modulation by Phosphorylation and All-trans Retinal
- •Synthesis, Maturation, and Targeting of CNG Channels
- •Visual Dysfunction Caused by Mutant CNG Channel Genes
- •References
- •Appendix
- •Visual Dysfunction Caused by Mutant CNG Channel Genes
- •Mutations in CNGA1 and CNGB1 Associated with Retinitis Pigmentosa
- •Mutations in CNGA3 and CNGB3 Associated with Cone Dysfunction
- •References
- •Rhodopsins in Drosophila Color Vision
- •Introduction
- •Anatomy and Molecular Aspects of Color-Sensitive Opsins in the Drosophila Eye
- •Structure of the Drosophila Eye: Ommatidia, Photoreceptors, and Rhodopsins
- •Molecular Genetics and Evolution of Rh5 and Rh6
- •Development and Patterning of Rhodopsins for Drosophila Color Vision
- •Mutually Exclusive Rhodopsin Expression
- •Transcription Factors Specify Outer from Inner Photoreceptors and Distinguish R7 from R8
- •A Stochastic Decision Induces Rhodopsins in R7 Photoreceptor
- •A Bistable Feedback Loop Specifies R8 Photoreceptor Subtype and Expression of Rh5 and Rh6
- •Comparison Between Mammalian and Drosophila Color Vision Rhodopsins
- •Human Color-Sensitive Opsins
- •Conclusion
- •References
- •INAD Signaling Complex of Drosophila Photoreceptors
- •Introduction
- •Identification of the INAD Signaling Complex
- •Function of the INAD Signaling Complex
- •Information Transfer From Rhodopsin to the Signaling Complex BY the Visual G Protein
- •Signaling Complexes in Vertebrate Photoreceptor Cells
- •Acknowledgments
- •References
- •Visual Signal Processing in the Inner Retina
- •Introduction
- •Visual Information is First Processed in the OPL
- •Bipolar Cells form Parallel Pathways and Provide Excitatory Input to the IPL
- •Functional Stratification of the IPL
- •ON and OFF Response Stratification
- •Sustained and Transient Response Stratification
- •Synaptic Mechanisms Shape Excitatory Signals in the IPL
- •Glutamate Release Is Tonic and Graded
- •Transporters Terminate Excitatory Signaling to Ganglion Cells
- •Postsynaptic Glutamate Receptor Properties Shape Ganglion Cell Excitation
- •Modulating Glutamate Release Shapes Excitatory Responses
- •Amacrine Cells Mediate Inhibition in the IPL
- •Presynaptic Inhibition
- •Asymmetric Presynaptic Inhibition
- •Presynaptic Inhibition Is Filtered by GABA Receptor Properties
- •Presynaptic Inhibition May Be Shaped by Transmitter Release Differences
- •Glycine, the Other Inhibitory Transmitter
- •Parallel Ganglion Cell Output Pathways
- •Ganglion Cells Encode Color Information
- •Directional-Selective Ganglion Cells
- •Intrinsically Photosensitive Ganglion Cells
- •Conclusions
- •References
- •Human Cone Spectral Sensitivities and Color Vision Deficiencies
- •Introduction
- •Overview
- •Transduction
- •Univariance, Monochromacy, Dichromacy, and Trichromacy
- •Trichromacy and Color-Matching Functions
- •Cone Spectral Sensitivities
- •Introduction
- •Cone Spectral Sensitivity Measurements
- •From Cone Spectral Sensitivities to Color-Matching Functions
- •Other Factors That Influence Spectral Sensitivity
- •Lens Pigment
- •Macular Pigment
- •Photopigment Optical Density
- •Changes with Eccentricity
- •Congenital Color Vision Deficiencies
- •Protan and Deutan Defects
- •Protanopia and Deuteranopia
- •Photopigment Variability and Protanomaly and Deuteranomaly
- •Tritanopia
- •Monochromacies
- •Cone Monochromacies
- •Rod Monochromacy
- •Conclusions
- •Acknowledgment
- •References
- •Luminous Efficiency Functions
- •Introduction
- •The Need for Luminous Efficiency
- •Psychophysical Measures of Luminous Efficiency
- •Factors that Influence Luminous Efficiency
- •Scotopic (Rod) Luminous Efficiency Function
- •Introduction
- •Univariance
- •International Standard
- •Photopic (Cone) Luminous Efficiency Function
- •Introduction
- •International Standards
- •Other Photopic (Nonadditive) Luminous Efficiency Functions
- •Mesopic (Rod-Cone) Luminous Efficiency Functions
- •Introduction
- •Models of Mesopic Luminous Efficiency
- •International Standard
- •Individual Differences Influencing Luminous Efficiency
- •Attenuation of Spectral Light by the Lens and Other Ocular Media
- •Attenuation of Spectral Light by the Macular Pigment
- •Optical Densities of the Photopigments
- •Relative Numbers of L and M Cones
- •Cone Pigment Polymorphisms
- •Directional Sensitivity
- •Variations in the Contribution of Chromatic Channels
- •Conclusions
- •References
- •Cone Pigments and Vision in the Mouse
- •Introduction
- •Prevalence and Spatial Distribution of Mouse Cones
- •Mouse Strain Variations
- •Mouse Cone Pigments
- •Cone Pigment Spectra
- •Evolution and Spectral Tuning of Mouse Cone Pigments
- •Regional Distribution of Mouse Cone Pigments
- •Expression of Mouse Cone Pigments
- •Cone Signal Pathways in the Mouse Retina
- •Cone-Based Vision in Mice
- •Assessment Techniques
- •Spectral Sensitivity
- •Spatial and Temporal Sensitivity
- •Color Vision
- •Targeted Deletions of Rods or Cones
- •Addition of New Cone Pigments
- •Mouse and Human Cone Vision
- •Acknowledgment
- •References
- •Multifocal Oscillatory Potentials of the Human Retina
- •Introduction
- •Recording Techniques
- •Underlying Mechanisms
- •The Influence of age and Gender
- •Disease-Related Changes
- •Origins of Single Potentials
- •Dichromats
- •Congenital Stationary Night Blindness
- •Topographical Alterations
- •Diabetes
- •Retinal Vessel Occlusion
- •Glaucoma
- •General Alterations
- •Vigabatrin Treatment
- •Conclusion
- •References
- •The Aging of the Retina
- •Introduction
- •Morphological Alterations
- •Neural Changes
- •Retinal Pigment Epithelium and Lipofuscin Formation
- •Bruch’s Membrane and Choroid
- •Retinal Function Changes
- •Age-Related Macular Disease
- •Conclusions
- •References
- •Aging of the Retinal Pigment Epithelium
- •Introduction
- •Aging Changes In the Fundus
- •Age-Related Changes In RPE Morphology
- •Melanosomes
- •Lipofuscin
- •Pigment Complexes
- •Mitochondria
- •Bruch’s Membrane
- •Functional Consequences of RPE Cell Aging
- •Phagocytic Load
- •The Effect of Lipofuscin on the RPE
- •Melanosomes
- •Antioxidant Capacity of the RPE
- •Lysosomal Enzyme Activity
- •Mitochondrial Damage in the RPE
- •Bruch’s Membrane Aging
- •Oxidative Stress and RPE Aging
- •The Relationship Between Aging and Retinal Pathologies
- •Summary and Conclusions
- •References
- •Visual Transduction and Age-Related Changes in Lipofuscin
- •Introduction: What is Lipofuscin?
- •Lipofuscin of the Retinal Pigment Epithelium
- •Composition of RPE Lipofuscin
- •Fluorescence Properties of RPE Lipofuscin
- •A2E as a Marker of Lipofuscin Accumulation
- •Factors Affecting Accumulation of RPE Lipofuscin
- •Phagocytosis and Autophagy
- •Role of Lysosomal Degradation
- •Role of Oxidative Stress
- •Role of Phototransduction in Accumulation of RPE Lipofuscin
- •Transient Buildup of All-trans Retinal in Photoreceptor Outer Segments as a Critical Factor for Lipofuscin Formation
- •Inhibition of the Retinoid Cycle Inhibits Lipofuscin Accumulation
- •Role of Exposure of the Retina to Light
- •Other Factors Contributing to Accelerated Accumulation of RPE Lipofuscin
- •A Hypothetical Scenario of Biogenesis of RPE Lipofuscin
- •Effects of Lipofuscin on RPE Function and Viability
- •Photoreactivity of RPE Lipofuscin
- •Toxicity of RPE Lipofuscin
- •Effects of Lipofuscin Components and Oxidative Stress in the RPE on Proinflammatory and Angiogenic Signaling
- •Approaches to Diminish Lipofuscin Accumulation or Lipofuscin-Induced Damage
- •Conclusions
- •References
- •A Nonspecific System Provides Nonphotic Information for the Biological Clock
- •Introduction
- •Nonphotic Information
- •Nonspecific Systems
- •Ascending Reticular-Activating System
- •Orexin/Hypocretin Projection
- •Intergeniculate Leaflet of the Thalamus
- •Anatomy
- •The Pharmacology of the IGL
- •Chronobiology
- •The Electrophysiology of the IGL
- •IGL as an Integrator of Photic and Nonphotic Information
- •Conclusions
- •References
- •The Circadian Clock: Physiology, Genes, and Disease
- •Introduction
- •Circadian Rhythms in Physiology and Behavior
- •Circadian Rhythms in Visual Function
- •Entrainment
- •Anatomy
- •The Suprachiasmatic Nucleus
- •Inputs to the SCN
- •Peripheral Oscillators
- •A Clock in the Eye
- •Oscillators Outside the Nervous System
- •Clock Genes
- •Human Implications
- •Summary
- •References
416 |
Boulton |
complicated by the regional variations in the structure and function of RPE cells and the paucity of relevant animal models. However, studies in mice clearly demonstrated that genetic or dietary manipulation can cause an AMD-like pathology in aged animals but not in young animals [96, 97].
SUMMARY AND CONCLUSIONS
This review documented age-related changes within the RPE and examined some of the casual mechanisms that result in such changes. However, despite considerable research, there is no general agreement about the fundamental cause or causes of aging.
REFERENCES
1.Boulton, M., Ageing of the retinal pigment epithelium, in Progress in retinal research, N. Osborne and G. Chader, eds. Oxford, UK: Pergamon; 1991:125–151.
2.Marmor, F., T.J. Wolfensberger, The retinal pigment epithelium. New York: Oxford University Press; 1998.
3.Hogan, M.J., J.A. Alvarado, J.E. Weddell, Histology of the human eye. Philadelphia: Saunders; 1971.
4.Boulton, M., P. Dayhaw-Barker, The role of the retinal pigment epithelium: topographical variation and ageing changes. Eye, 2001;15(Pt 3):384–389.
5.Streeten, B.W., Development of the human retinal pigment epithelium and the posterior segment. Arch Ophthalmol, 1969;81(3):383–394.
6.Marshall, J., The ageing retina: physiology or pathology? Eye, 1987;1:282–295.
7.Kanski, J., Clinical ophthalmology: a systematic approach. London: Butterworth-Heinemann; 2003.
8.Salvi, S.M., S. Akhtar, Z. Currie, Ageing changes in the eye. Postgrad Med J, 2006;82(971): 581–587.
9.Panda-Jonas, S., J.B. Jonas, M. Jakobczyk-Zmija, Retinal pigment epithelial cell count, distribution, and correlations in normal human eyes. Am J Ophthalmol, 1996;121(2):181–189.
10.Gao, H., J.G. Hollyfield, Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells. Invest Ophthalmol Vis Sci, 1992;33(1):1–17.
11.Dorey, C.K., et al., Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. Invest Ophthalmol Vis Sci, 1989;30(8):1691–1699.
12.Feeney-Burns, L., E.S. Hilderbrand, S. Eldridge, Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. Invest Ophthalmol Vis Sci, 1984;25(2):195–200.
13.Burke, J.M., L.M. Hjelmeland, Mosaicism of the retinal pigment epithelium: seeing the small picture. Mol Interv, 2005;5(4):241–249.
14.Weiter, J.J., et al., Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes. Invest Ophthalmol Vis Sci, 1986;27(2):145–152.
15.Sarna, T., Properties and function of the ocular melanin—a photophysical view. J Photochem Photobiol B Biol, 1992;12:215–258.
16.Boulton, M., et al., Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium. Vision Res, 1990;30(9):1291–1303.
17.Boulton, M., et al., The photoreactivity of ocular lipofuscin. Photochem Photobiol Sci, 2004;3(8):759–764.
Retinal Pigment Epithelium Aging |
417 |
18.Schutt, F., et al., Proteome analysis of lipofuscin in human retinal pigment epithelial cells. FEBS Lett, 2002;528(1–3):217–221.
19.Schutt, F., et al., Proteins modified by malondialdehyde, 4-hydroxynonenal, or advanced glycation end products in lipofuscin of human retinal pigment epithelium. Invest Ophthalmol Vis Sci, 2003;44(8):3663–3668.
20.Warburton, S., et al., Examining the proteins of functional retinal lipofuscin using proteomic analysis as a guide for understanding its origin. Mol Vis, 2005. 11:1122–1134.
21.Renganathan, K., K. Ng, M. Mavies, X. Gu, M. Rozanowska, M. Rayborn, R.G. Salmon, J.G. Hollyfield, M.E. Boulton, J.W. Crabb. Does lipofuscin contain protein? Amino acid, protein and ultrastructural analysis of human lipofuscin. Invest Ophthalmol Vis Sci 2007; 48: ARVO E-abstract 5059.
22.Clancy, K.M.R., et al., Atomic force microscopy and near-field scanning optical microscopy measurements of single human retinal lipofuscin granules. J Phys Chem B, 2000;104: 12098–12101.
23.Haralampus-Grynaviski, N.M., et al., Probing the spatial dependence of the emission spectrum of single human retinal lipofuscin granules using near-field scanning optical microscopy. Photochem Photobiol, 2001;74(2):364–368.
24.Feeney, L., Lipofuscin and melanin of human retinal pigment epithelium. Fluorescence, enzyme cytochemical, and ultrastructural studies. Invest Ophthalmol Vis Sci, 1978;17(7): 583–600.
25.Feher, J., et al., Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration. Neurobiol Aging, 2006;27(7):983–993.
26.de Jong, P.T., Age-related macular degeneration. N Engl J Med, 2006;355(14):1474–1485.
27.Guymer, R., P. Luthert, A. Bird, Changes in Bruch’s membrane and related structures with age. Prog Retin Eye Res, 1999;18(1):59–90.
28.Bird, A.C., Doyne lecture. Pathogenesis of retinal pigment epithelial detachment in the elderly; the relevance of Bruch’s membrane change. Eye, 1991;5:1–12.
29.Marshall, J., et al., Aging and Bruch’s membrane, in The retinal pigment epithelium, M.F. Marmor and T.J. Wolfensberger, eds. New York: Oxford University Press; 1998: 669–692.
30.Chong, N.H., et al., Decreased thickness and integrity of the macular elastic layer of Bruch’s membrane correspond to the distribution of lesions associated with age-related macular degeneration. Am J Pathol, 2005;166(1):241–251.
31.Ugarte, M., A.A. Hussain, J. Marshall, An experimental study of the elastic properties of the human Bruch’s membrane-choroid complex: relevance to ageing. Br J Ophthalmol, 2006;90(5):621–626.
32.Handa, J.T., et al., Increase in the advanced glycation end product pentosidine in Bruch’s membrane with age. Invest Ophthalmol Vis Sci, 1999;40(3):775–779.
33.Hageman, G.S., R.F. Mullins, Molecular composition of drusen as related to substructural phenotype. Mol Vis, 1999;5:28.
34.Curcio, C.A., et al., Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina. Invest Ophthalmol Vis Sci, 1993;34(12):3278–3296.
35.Jackson, G.R., C. Owsley, and C.A. Curcio, Photoreceptor degeneration and dysfunction in aging and age-related maculopathy. Ageing Res Rev, 2002;1(3):381–396.
36.Rozanowska, M., et al., Blue light-induced reactivity of retinal age pigment. In vitro generation of oxygen-reactive species. J Biol Chem, 1995;270(32):18825–18830.
37.Rozanowska, M., et al., Blue light-induced singlet oxygen generation by retinal lipofuscin in non-polar media. Free Radic Biol Med, 1998;24(7–8):1107–1112.
418 |
Boulton |
38.Gaillard, E.R., et al., Photophysical studies on human retinal lipofuscin. Photochem Photobiol, 1995;61(5):448–453.
39.Davies, S., et al., Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells. Free Radic Biol Med, 2001;31(2):256–265.
40.Shamsi, F.A., M. Boulton, Inhibition of RPE lysosomal and antioxidant activity by the age pigment lipofuscin. Invest Ophthalmol Vis Sci, 2001;42(12):3041–3046.
41.Godley, B.F., et al., Blue light induces mitochondrial DNA damage and free radical production in epithelial cells. J Biol Chem, 2005;280(22):21061–21066.
42.Schutt, F., et al., Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci, 2000;41(8):2303–2308.
43.Sparrow, J.R., B. Cai, Blue light-induced apoptosis of A2E-containing RPE: involvement of caspase-3 and protection by Bcl-2. Invest Ophthalmol Vis Sci, 2001;42(6):1356–1362.
44.Sparrow, J.R., K. Nakanishi, C.A. Parish, The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci, 2000;41(7):1981–1989.
45.Pawlak, A., et al., Comparison of the aerobic photoreactivity of A2E with its precursor retinal. Photochem Photobiol, 2003;77(3):253–258.
46.Rozanowska, M., T. Sarna, Light-induced damage to the retina: role of rhodopsin chromophore revisited. Photochem Photobiol, 2005;81(6):1305–1330.
47.Ben-Shabat, S., et al., Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvement. Angew Chem Int Ed Engl, 2002;41(5):814–817.
48.Zhou, J., et al., Mechanisms for the induction of HNEMDA- and AGE-adducts, RAGE and VEGF in retinal pigment epithelial cells. Exp Eye Res, 2005;80(4):567–580.
49.Zhou, J., et al., Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Proc Natl Acad Sci U S A, 2006;103(44):16182–16187.
50.Rozanowska, M., et al., Photoreactivity of aged human RPE melanosomes: a comparison with lipofuscin. Invest Ophthalmol Vis Sci, 2002;43(7):2088–2096.
51.Rozanowski, B., J. Cuenco, S. Davies, F.A. Shamsi, A. Zadlo, P. Dayhaw-Barker, M. Rozanowska, T. Sarna, M.E. Boulton (2007) The phototoxicity of aged human retinal melanosomes. Photochem Photobiol. 2007 Dec 17; [Epub ahead of print]
52.Zarbin, M.A., Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol, 2004;122(4):598–614.
53.Winkler, B.S., et al., Oxidative damage and age-related macular degeneration. Mol Vis, 1999;5:32.
54.Beatty, S., et al., The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol, 2000;45(2):115–134.
55.Friedrichson, T., et al., Vitamin E in macular and peripheral tissues of the human eye. Curr Eye Res, 1995;14(8):693–701.
56.Liles, M.R., D.A. Newsome, P.D. Oliver, Antioxidant enzymes in the aging human retinal pigment epithelium. Arch Ophthalmol, 1991;109(9):1285–1288.
57.Castorina, C., et al., Lipid peroxidation and antioxidant enzymatic systems in rat retina as a function of age. Neurochem Res, 1992;17(6):599–604.
58.Beatty, S., et al., Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci, 2001;42(2):439–446.
59.Maeda, A., J.W. Crabb, and K. Palczewski, Microsomal glutathione S-transferase 1 in the retinal pigment epithelium: protection against oxidative stress and a potential role in aging. Biochemistry, 2005;44(2):480–489.
Retinal Pigment Epithelium Aging |
419 |
60.Organisciak, D., et al., Genetic, age and light mediated effects on crystallin protein expression in the retina. Photochem Photobiol, 2006;82(4):1088–1096.
61.Liao, J.H., J.S. Lee, S.H. Chiou, C-terminal lysine truncation increases thermostability and enhances chaperone-like function of porcine alphaB-crystallin. Biochem Biophys Res Commun, 2002;297(2):309–316.
62.Imamura, Y., et al., Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration. Proc Natl Acad Sci U S A, 2006;103(30):11282–11287.
63.Boulton, M., et al., Regional variation and age-related changes of lysosomal enzymes in the human retinal pigment epithelium. Br J Ophthalmol, 1994;78(2):125–129.
64.Ogawa, T., et al., Changes in the spatial expression of genes with aging in the mouse RPE/ choroid. Mol Vis, 2005;11:380–386.
65.Liang, F.Q., B.F. Godley, Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration. Exp Eye Res, 2003;76(4):397–403.
66.Godley, B.F., F.Q. Liang, Topographical and age-related variations in human RPE response to oxidative stress. Invest Ophthalmol Vis Sci, 2003;44:ARVO E-abstract 1645.
67.Godley, B.F., R. Alsaadi, F.Q. Liang, Increased oxidative stress in human macular RPE cells. Invest Ophthalmol Vis Sci, 2005;46:ARVO E-abstract 5288.
68.Hillenkamp, J., et al., The influence of path length and matrix components on ageing characteristics of transport between the choroid and the outer retina. Invest Ophthalmol Vis Sci, 2004;45(5):1493–1498.
69.Curcio, C.A., et al., Esterified and unesterified cholesterol in drusen and basal deposits of eyes with age-related maculopathy. Exp Eye Res, 2005;81(6):731–741.
70.Pauleikhoff, D., et al., Aging changes in Bruch’s membrane. A histochemical and morphologic study. Ophthalmology, 1990;97(2):171–178.
71.Moore, D.J., A.A. Hussain, and J. Marshall, Age-related variation in the hydraulic conductivity of Bruch’s membrane. Invest Ophthalmol Vis Sci, 1995;36(7):1290–1297.
72.Cai, H., L.V. Del Priore, Bruch membrane aging alters the gene expression profile of human retinal pigment epithelium. Curr Eye Res, 2006;31(2):181–189.
73.Yamada, Y., et al., The expression of advanced glycation endproduct receptors in rpe cells associated with basal deposits in human maculas. Exp Eye Res, 2006;82(5): 840–848.
74.Tian, J., et al., Advanced glycation endproduct-induced aging of the retinal pigment epithelium and choroid: a comprehensive transcriptional response. Proc Natl Acad Sci U S A, 2005;102(33):11846–11851.
75.Gullapalli, V.K., et al., Retinal pigment epithelium resurfacing of aged submacular human Bruch’s membrane. Trans Am Ophthalmol Soc, 2004;102:123–137; discussion 137–138.
76.Halliwell, B., J.M. Gutteridge, Free radicals in biology and medicine. 3rd ed. New York: Oxford University Press; 1999.
77.Harman, D., The biologic clock: the mitochondria? J Am Geriatr Soc, 1972;20(4):145–147.
78.Terman, A., U.T. Brunk, Oxidative stress, accumulation of biological “garbage,” and aging. Antioxid Redox Signal, 2006;8(1–2):197–204.
79.Mayer, B., Nitric oxide. New York: Springer; 2000.
80.Rubbo, H., C. Batthyany, R. Radi, Nitric oxide-oxygen radicals interactions in atherosclerosis. Biol Res, 2000;33(2):167–175.
81.Min, D.B., J.M. Boff, Chemistry and reaction of singlet oxygen in foods. Comp Rev Food Sci Food Safety, 2002;1:58–72.
420 |
Boulton |
82.Linnane, A.W., H. Eastwood, Cellular redox regulation and prooxidant signaling systems: a new perspective on the free radical theory of aging. Ann N Y Acad Sci, 2006;1067:47–55.
83.Miceli, M.V., M.R. Liles, D.A. Newsome, Evaluation of oxidative processes in human pigment epithelial cells associated with retinal outer segment phagocytosis. Exp Cell Res, 1994;214(1):242–249.
84.Cai, J., et al., Oxidative damage and protection of the RPE. Prog Retin Eye Res, 2000;19: 205–221.
85.Dunford, R., et al., Interaction of melanin with carbonand oxygen-centered radicals from methanol and ethanol. Free Radic Biol Med, 1995;19:735–740.
86.Edge, R., et al., Carotenoid radicals-melanin interactions. J Phys Chem, 2000;104: 7193–7196.
87.Rozanowska, M., et al., Free radical scavenging properties of melanin interaction of euand pheo-melanin models with reducing and oxidising radicals. Free Radic Biol Med, 1999. 26(5–6):518–525.
88.Zareba, M., et al., Oxidative stress in ARPE-19 cultures: do melanosomes confer cytoprotection? Free Radic Biol Med, 2006;40(1):87–100.
89.Jarrett, S.G., J. Albon, M. Boulton, The contribution of DNA repair and antioxidants in determining cell type-specific resistance to oxidative stress. Free Radic Res, 2006;40(11): 1155–1165.
90.Crawford, D.R., K.J. Davies, Adaptive response and oxidative stress. Environ Health Perspect, 1994;102(Suppl 10):25–28.
91.Jarrett, S.G., M.E. Boulton, Antioxidant up-regulation and increased nuclear DNA protection play key roles in adaptation to oxidative stress in epithelial cells. Free Radic Biol Med, 2005;38(10):1382–1391.
92.Bird, A., J. Marshall, Retinal pigment epithelial detachments in the elderly. Trans Ophthalmol Soc UK, 1986;105:674–682.
93.Archer, D., Retinal neovascularization. Trans Ophthalmol Soc UK, 1983;103:2–26.
94.Eagle, R.C., Jr., Mechanisms of maculopathy. Ophthalmology, 1984;91(6):613–625.
95.Bird, A., J. Marshall, Retinal receptor disorders without known metabolic abnormalities., in Pathobiology of ocular disease, A. Garner and G. Klintworth, eds. New York: Dekker; 1982:1167–1220.
96.Ambati, J., et al., An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat Med, 2003;9(11):1390–1397.
97.Malek, G., et al., Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration. Proc Natl Acad Sci U S A, 2005;102(33):11900–11905.
98.Rahman, I., S.K. Biswas, A. Kode, Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol, 2006;533:222–239.