Abstract
Abstract: :
Purpose:Latanoprost is a prostaglandin F2 alpha analogue, which has a decreasing effect on intraocular pressure. This study examines whether latanoprost prevents retinal ganglion cell (RGC) death induced by N–Methyl–D–Aspartate (NMDA) or optic nerve axotomy. Methods:RGC death of adult Sprague–Dawley (SD) rats was induced by intravitreal administration of NMDA (20 nmol/eye) or optic nerve axotomy. Latanoprost at the doses of 3, 30, 300 nmol/eye were administrated intravitreally 15 minutes before NMDA injection or optic nerve axotomy. Retinal damage was estimated by counting ganglion cells retrogradely labeled by fluorogold. Seven days after NMDA injury or 10 days after optic nerve axotomy, retinas were sampled and 12 distinct areas of whole–mounted retina were counted. We analyzed the average value of the two investigators statistically with Scheffe’s multiple range tests. For the purpose of the in vitro experiment, we isolated the RGCs by two–step panning method. A series of doses of latanoprost acid (10 nM, 100 nM, 1 µM, and 10 µM) was administrated to the culture medium for 48 h and the survival rate of RGCs was evaluated using flow cytometry as previously reported. Results:Seven days after NMDA injury, the number of fluorogold labeled RGCs was 555.5 ± 122.0 cells/mm2 (n=7) by the vehicle administration. By the latanoprost administration (3, 30, 300 nmol/eye), the number of labeled RGCs was 606.1 ± 145.4 (n=7), 846.0 ± 177.5 (n=6), 829.9 ± 140.3 cells/mm2 (n=6), respectively. The number of labeled RGCs significantly increased at the dose of 30 and 300 nmol/eye of latanoprost (P=0.0166, 0.252). Ten days after optic nerve axotomy, the number of fluorogold labeled RGCs was 461.5 ± 74.9 cells/mm2 (n=8) by the vehicle administration. By the administration of latanoprost (0.03, 0.3, 3, 30, 300 nmol/eye), the number of fluorogold labeled RGCs was 580.2 ± 97.9 (n=5), 814.5 ± 236.7 (n=5), 796.5 ± 254.6 (n=6), 875.6 ± 106.7 (n=6), 1160.1 ± 170.5 cells/mm2 (n=7), each. The number of labeled RGCs significantly increased over 0.3 nmol/eye of latanoprost (P=0.035), compared with vehicle control. However, latanoprost acid had no effects on purified RGCs at any investigated concentration. Conclusions:Latanoprost has a neuroprotective effect on NMDA or optic nerve axotomy induced RGC death.
Keywords: ganglion cells • neuroprotection • excitatory neurotransmitters