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Abstract #15314 Published in IGR 8-4
Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase
Nakanishi Y; Nakamura M; Mukuno H; Kanamori A; Seigel GM; Negi AExperimental Eye Research 2006; 83: 1108-1117
The purpose of this study was to investigate whether latanoprost, a prostaglandin F2α analogue, has a direct anti-apoptotic effect both in retinal neuro-glial cells in culture and in diabetic retina. R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24h serum deprivation. Serum withdrawal made up to 15% of R28 cells pyknotic and activated caspase-3 immunoreactive, and latanoprost acid suppressed apoptosis with dose dependency at an optimum concentration of 1.0 μM (P < 0.001). UO126, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) 1 and 2 inhibitor reversed this effect. Streptozotocin induced one- or three-month diabetic rats received balanced-salt-solution (BSS) in the left eye and latanoprost eye drops in the right for 5 days. Retinal wholemount was subjected to terminal dUTP nick end labeling (TUNEL) staining, whereas eyeballs were enucleated for cleaved caspase-3 immunofluorescence. Retinal homogenates were probed for phospho- or total p44/p42 MAPK and Akt. One- and three-month diabetic retina had 30.2 ± 15.3 and 23.6 ± 9.0 TUNEL positive cells per 0.5 cm2 , respectively, whereas control retina had few TUNEL positive cells. Latanoprost instillation significantly reduced these cells (10.0 ± 3.1 and 11.3 ± 3.1 cells per 0.5 cm2 for 1M and 3M, respectively, P < 0.01), whereas BSS did not. Latanoprost also significantly reduced cleaved caspase-3 immunoreactive cells in ganglion cell and inner nuclear layers (P < 0.05). Latanoprost increased phosphorylated to total protein ratio of p44/p42 MAPK (P < 0.05), but not of Akt. Taken together, the present findings suggest that latanoprost rescues retinal neurons and/or glial cells from apoptosis, which is probably mediated by p44/p42 MAPK through caspase-3 inhibition.
Dr. Y. Nakanishi, Division of Ophthalmology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
3.3 Immunohistochemistry (Part of: 3 Laboratory methods)
5 Experimental glaucoma; animal models
