Death and neuroprotection of retinal ganglion cells after different types of injury

Abstract

In adult Sprague-Dawley rats, retinal ganglion cell survival was investigated after intraorbital optic nerve section and after transient ischemia of the retina induced by elevation of the intraocular pressure or by selective ligature of the ophthalmic vessels. The thickness of the inner nuclear and inner plexiform layers was also assessed after transient periods (120 min) of retinal ischemia induced by selective ligature of the ophthalmic vessels. In addition, we have also investigated the neuroprotective effects of different substances in these paradigms. The intraocular injection of brain-derived neurotrophic factor increased RGC survival after retinal ischemia induced by elevation of the intraocular pressure or by selective ligature of the ophthalmic vessels. The caspase-inhibitor Z-DEVD increased retinal ganglion cell survival after optic nerve section and also after 90 min of retinal ischemia induced by selective ligature of the ophthalmic vessels. The peptide Bcl-2 did not increase retinal ganglion cell survival after optic nerve section but increased retinal ganglion cell survival after 60 or 90 min of retinal ischemia induced by selective ligature of the ophthalmic vessels. Finally, BDNF, nifedipine, naloxone and bcl-2 prevented in part the decrease in thickness of the inner nuclear layer and inner plexiform layer induced by selective ligature of the ophthalmic vessels. Our results suggest that retinal ganglion cell loss induced by different types of injury, may be prevented by substances with neuroprotective effects, by altering steps of the cascade of events leading to cell death.

Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats

“…We had not observed retinal holes in previous experiments in which we had carried out IVI of different substances, 40,51,67,77 but this may be related to the different size of the needle used for the present experiments. Thus, for our previous experiments, the perforation was made with a 30G needle and the IVI was made through a 34G needle, while in the present experiments, 27G and 26G needles were used for the same purposes.…”

“…51,67 The injections were made through the superotemporal sclera, where a perforating sclerotomy through the conjunctiva and sclera was made with a sterile 27-gauge (G) needle at approximately 1 to 2 mm from the limbus. Then, the needle of the Hamilton microsyringe (26G, Hamilton 701 N; Esslab, Benfleet, UK) was introduced first obliquely toward the optic nerve and later perpendicularly toward the center of the globe.…”

Neuroprotection of retinal ganglion cell function and their central nervous system targets

“…5,6 The models used can also be deployed to investigate a number of pathophysiological issues, including axonal regeneration, synapse formation, 7,8 injury-induced neuronal degeneration 9,10 and prevention of injury-induced neuronal degeneration (ie neuroprotection). 3,11 This paper examines some of the effects induced by transient ischaemia of the retina and how some of these may be prevented, diminished, or ameliorated.…”

Topical Treatment With Bromfenac Reduces Retinal Gliosis and Inflammation After Optic Nerve Crush

“…34,38,40,41 Moreover, this injury also triggers an important inflammatory response within the injured and contralateral fellow eye. 27,28,42 Optic nerve crush is a model that has been widely used to test neuroprotective therapies 36,37,41,[43][44][45][46][47] and to investigate the molecular events underlying central nervous system neuronal death upon axonal trauma. 25,48,49 Optic nerve crush is as well often used as a simplified model of glaucomatous injury.…”