For example, topically applied latanoprost reduced the number of apoptotic RGCs following optic nerve crush , while the drug also exerts a neuroprotective impact on cells challenged by glutamate toxicity . A variety of pathways to the anti-apoptotic impact of prostaglandin analogs are actually proposed . It has been recommended that latanoprost might possibly work by unfavorable feedback on neuronal COX-2 exercise, as it prevented lactate accumulation from the retinal tissue of animals subjected to acute ischemia . Also, this exact same research observed that COX-2 activity was lowered by both arachidonic acid and latanoprost in RGCs exposed to extra glutamate and that inhibition of inducible nitric oxide synthase occurred together with the identical drug concentrations. Latanoprost might possibly also exhibit a direct anti-apoptotic effect via neurite outgrowth and caspase-3 inhibition, mediated by p44/p42 mitogen-activated protein kinase .
There are numerous other hypotheses regarding secondary neuroprotective mechanisms for prostaglandin analogs, like effects on ocular and ONH hemodynamics . Carbonic anhydrase inhibitors are established as hypotensive agents, diuretics and antiepileptics, with further use while in the management of gastric and duodenal ulcers, MEK Inhibitor neurological problems and osteoporosis. CA-II is definitely the isoenzyme that plays a purpose in aqueous humor production inside the human anterior segment . Dorazolamide and brinzolamide each potently inhibit CA-II and significantly lessen aqueous ranges . By acting on CA-II, acetazolamides inhibition of sodium accession decreases bicarbonate formation within the ciliary epithelium .
Although CA exercise localizes histochemically during the retina to M¨1ller cells, cones along with the pigment epithelium , distribution from the CA inhibitor trifluormethazolamide in tissue showed high concentrations within the ciliary body . In retinal tissue in culture, the CA inhibitor Obatoclax dorzolamide decreased apoptotic pathways with publicity to methylglyoxal and glyoxal and H2O2 . This class of medications also demonstrates a vasodilatory effect , very likely through a mechanism similar to CO2-induced modifications . CA inhibitors improve cerebral blood flow following systemic administration , and ocular blood supply increases topical application . In addition, membrane-associated CA activity inside of neuronal processes is additionally most likely to modulate the pH of extracellular fluid, which can have an effect on metabolic activity .
Additionally, ocular pulse amplitude increases following dorzolamide administration . Even so, no adjustments were noted in ONH blood movement following dorzolamide administration in healthy human topics . A word on NMDA receptor antagonists NMDA receptor antagonists have acquired broad focus as probable neuroprotective agents by means of their suppression of probably excitotoxic pathways .