In retina, various studies indicate that the mitochondria in the photoreceptor’s inner segments are involved in the process of retinal degeneration.
28 31 41 42 43 Isolated retina exposed to high external Ca
2+ concentration has low ATP concentration and respiration level, and it undergoes rod degeneration.
31 41 In photoreceptors, mutations in phototransduction proteins (e.g., the
rd mouse with a mutation in phosphodiesterase, the GCAP Y99C mutation, and deletion of cGMP-gated channel) cause a variety of retinal degeneration diseases.
44 In other retinal neurons, especially ganglion cells, ischemia, diabetes, and mechanical damage trigger apoptotic events.
45 In all, or most of these cases, apoptosis appears to be promoted by an abnormal concentration of intracellular Ca
2+.
44 The relationship between changes in Ca
2+ concentration and mitochondria dysfunction is well established.
3 Ca
2+ accumulated in the mitochondria, activates PTP; leading to mitochondrial swelling, and triggering an apoptotic event.
28 43 If, as suggested, the site of Ca
2+ action is within the mitochondria, on the matrix side of the inner mitochondria membrane,
43 then Ca
2+ must first cross the outer mitochondrial membrane. VDAC is permeable to Ca
2+, and it possesses Ca
2+ binding sites.
23 Thus, VDAC, as a component of the PTP,
3 5 23 46 47 48 49 50 may be involved in inducing mitochondrial swelling. This, together with its being highly localized to photoreceptors and some ganglion cell mitochondria, implies that it is most likely to participate in apoptotic events in these particular cells. In summary, VDAC may play a key role in processes of retinal degeneration that result from ATP depletion and Ca
2+ overload.