Retinal degeneration, mechanisms

Hollyfield, JG, Salomon, RG, and Crabb, JW, 2003. Proteomic approaches to understanding age-related macular degeneration, In LaVail, MM, Anderson, RE, and Hollyfield, JG (Eds.), Retinal Degenerations Mechanisms and Experimental Therapy. Kluwer Academic/Plenum Publishers, New York, pp. 83-89. 

Wenzel, A., Grimm, C., Samardzija, M., Reme, C.E., 2005. Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Ret Eye Res. 24, 275-306. 

The decreased behavioural photoresponsiveness in cryptochrome-mutant mice is somewhat difficult to interpret since these mice also lack free-running circadian rhythms. Therefore, one is measuring masking, not circadian responses. Although masking is also preserved in retinal-degenerate animals (Mrosovsky et al 2000), the neural and molecular mechanisms of masking are not as well understood as those of circadian rhythms. 

Development of culture systems in which distribution of various neurons could be studied under controlled conditions contributes to our understanding of these mechanisms. However, such experiments need reliable methods of labeling live neurons. Moreover, information regarding how the retinal mosaics respond to various pathological conditions, such as retinal degeneration (Sharma, 2001a, b Sharma et al., 2001), enhances our understanding of mosaic formation and compensatory mechanisms that may reside in the retina. 

Liang, F.Q., and Godley, B.F. 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., 76,397-403, 2003. 

Disorders of the posterior segment of the eye are particularly difficult to treat. The efficient clearance mechanisms at the front of the eye reduce the concentrations of drug able to diffuse to the back of the eye. Futhermore, many of these disorders are chronic conditions, requiring continuous therapy. The diseases of the back of the eye include Cytomeaglovirus retinits (CMVR), Proliferative vitreoretinopathy (PVR), diabetic retinopathy, age-rated macular degeneration, endophthalmitis and retinitis pigmentosa. 

There is also evidence from animal models that brimonidine may provide neuroprotective properties that could spare retinal ganglion cells and the optic nerve. Using different models to achieve neuronal insult, including mechanical and acute retinal ischemic/reperfu-sion injury, brimonidine appears to protect the optic nerve and retinal ganglion cells from further degeneration. 

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