Analysis of aberrant retinal neuro-glial relationship in glaucoma and diabetic retinopathy

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Chronic ocular hypertension (COH) was made in rat by episcleral vein cauterization to induce apoptosis of retinal ganglion cells (RGC). We found that the insulin / IGF-1/ Akt pathway was activated to counteract apoptosis in retina of this model. This finding suggests that an anti-apoptotic signal may be intrinsically activated I glaucomatous retina, although the magnitude of its activation is not enough to inhibit the development of RGC apoptosis. We also found characteristic changes in glial reactivity in the retina with COH. Glial fibrillary acidic protein, which expression is normally confined to astrocytes, was expressed in Muller cells in eyes with COH. The altered expression continued after normalization of intraocular pressure and occurred in the contralateral eyes in the long-term follow-up. Autoimmunity has been implicated in the development of glaucomatous optic neuropathy, although the mechanism is still unknown. The above observation indicates the possibility that the elevated intraocular pressure in one eye may affect the glial function in the contralateral eye by immunological responses through yet unidentified mechanisms.Accelerated apoptosis of retinal neurons and altered glial reactivity are reportedly observed in diabetic retina even before the development of microangiopathy as well. Mounting evidence shows that a variety of topical ocular hypotensives not only reduces intraouclar pressure but also exerts a neuroprotective effect in retina. In retina of streptozotocin-induced diabetic rat, immunoreactivity of activated caspase 3 and neuronal apopotosis were increased, which were reversed when latanoprost, a prostaglandin F2 alpha analogue, was topically administered. Latanoprost specifically enhanced phosphorylation of p44/p42 rnitogen activated protein kinase, but not of Akt, in retina. These findings open a new avenue of possible pharmacological intervention to inhibit the neurodegenerative changes in diabetic retinopathy.