Melanopsin-Containing or Non-Melanopsin-Containing Retinal Ganglion Cells Response to Acute Ocular Hypertension With or Without Brain-Derived Neurotrophic Factor Neuroprotection

Abstract

PURPOSE: To analyze the responses of different retinal ganglion cell (RGC) types to acute ocular hypertension (AOH) and intravitreal administration of brain-derived neurotrophic factor (BDNF). METHODS: In adult albino rats, the anterior chamber of the left eye was cannulated with a needle connected to a saline container elevated 1½ meters above the eye for 75 minutes. Rats received 12 hours before a 5 ?l intravitreal injection containing 5 ?g BDNF in 1% albumin PBS or vehicle and were analyzed 3, 7, 14, or 45 days later. Both retinas were dissected as wholemounts and immunolabeled for melanopsin (to identify intrinsically photosensitive RGCs) or Brn3a (to identify all RGCs except melanopsin +RGCs). RESULTS: During AOH there is ischemic damage and mechanical eye-globe deformation. Acute ocular hypertension results in a progressive loss of Brn3a+RGCs in the vehicle-treated retinas (39%, 35%, 25%, and 13% of the original value, at 3, 7, 14, or 45 days, respectively), whereas BDNF increases their survival to 81%, 73%, 59%, or 57% at the same time periods. In vehicle-treated retinas, 37% or 39% of m+RGCs survive at 14 or 45 days, respectively, whereas BDNF treatment increases their survival to 40% or 78% at the same time points. CONCLUSIONS: Different types of RGCs respond differently to AOH because Brn3a+RGCs die progressively, but m+RGCs do not. After a transient downregulation of melanopsin expression, their number remains constant and their survival is proportionally higher than that of Brn3a+RGCs. BDNF affords a permanent protection up to 45 days after AOH injury in both types of RGCs.