LITHIUM CHLORIDE RESCUES RETINAL GANGLION CELLS IN RAT MODEL OF GLUTAMATE EXCITOTOXICITY

Retinal ganglion cell (RGC) death is distinctive of many ophthalmic disorders, such as glaucoma, optic neuropathies, and various retinovascular diseases. N-methyl-D-aspartate (NMDA)-type glutamate receptor (NMDAR)-mediated excitotoxicity is thought to be an important contributor to RGC death. Uninterrupted activation of a large number of NMDARs leads to increases in intracellular calcium loads, initiating a cascade of events that eventually result in apoptosis or necrosis. We aim to prevent or delay RGC death by an intervention involving lithium to afford neuroprotection of RGCs or neutralization of the deleterious effects of toxic factors. Existing reports highlight a range of lithium dosage applied from 7 to 21 days to promote the survival of RGCs damaged by optic nerve injury. Lithium was injected continuously for 7 days at a dose of 30, 50, and 70 mg/kg body weight (b.w.) to Wistar rats after injecting 20 mM NMDA intravitreally. Morphological changes observed by hematoxylin and eosin (H & E) staining along with measurement of the thickness of the inner retina (IR) , made up of ganglion cell complex (GCC), showed an increase in neuroprotection of RGCs in increasing order of dosage of lithium chloride after exposure to NMDA. Ultrastructure changes seen by transmission electron microscopy (TEM) showed necrosis, rupture of the membrane after NMDA insult, which was again overcome by increasing doses of lithium chloride with the best results observed at the highest dose of 70 mg/kg. Since early morphological changes of RGCs and their subsequent death are indicators of glaucoma, the present study indicates that the prevention of RGC loss by lithium in controlled dosage can lead to affordable neuroprotection against excitotoxicity.