Τόμος 25 (2007) – Τεύχος 1 – Άρθρο 19 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 25 (2007) – Issue 1– Article 19 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

Πρόκληση in vivo Ισχαιμίας με Διεγερτικά Αμινοξέα και Μελέτη της Προστατευτικής Δράσης της Σωματοστατίνης στον Αμφιβληστροειδή του Αρουραίου

Neuroprotective Role of Soma­tostatin in an in vivo Model of Retinal Ischemia

Ελληνικά – Greek

Άρθρο

Article

Retinal ischemia is the underlying cause of many ocular diseases and leads to neuronal dam­age and blindness. Somatostatin has been shown to have neuroprotective effects in different paradigms of neurotoxicity in the central nervous system, such as NMDA-induced neurotoxicity in cortical cultures and in middle cerebral artery occlusion. Somatostatin and its sst₂ agonists inhibited the ischemia-induced neovas­cularization and protected the retina in a rat model of chemical ischemia. The aim of the present study was to develop an in vivo model of excitotoxicity-induced ischemia in the retina and to investigate the neuropro­tective effect of somatostatin and its analogs. Adult female and male Sprague Dawley (250-300 g) or Brown Norway (150-200 g) rats were employed. The housing conditions and all procedures employed were in accordance to the European Communities Council Directive (86/609/EEC). The excitatory amino acids AMPA (42 nmol/eye) or NMDA (42 nmol/eye) were injected intravitreally in one eye, while the other eye received PBS (50 mM). The animals that received AMPA (42 nmol) were euthanized after 1, 2, 4, 8, 16 and 30 days, those that received NMDA (42 nmol) were euthanized after 1 or 8 days. A group of animals received AMPA (42 nmol) and the sst₂ analog L-779, 976 (10^-5M or 10^-4M) and was euthanized after 1 day. Immunohistochemical studies were employed to ex­amine retinal cell loss. These demonstrated the loss of retinal cholinergic amacrine cells [ChAT immunoreac­tivity (IR)] in the AMPA (42 nmol) treated groups from the 1^st till the 30^th day post injection. The NMDA treat­ment decreased the number of the ChAT-IR cells at the 1^st day but had no effect at 8^th day after the injec­tion. In addition, AMPA (42 nmol) caused a substantial loss of bNOS-expressing amacrine cells at the 1^st day after treatment. In contrast, other retinal cells such as rod and cone bipolar cells (PKC and recoverin IR, respectively), ganglion cells (MAP1A IR) and their axons (NF-L IR) and the dopaminergic cells (TH IR) were not affected by the AMPA (42 nmol) treatment. TUNEL staining confirmed the AMPA-induced retinal ischemia. The sst₂ analog L-779, 976 (10^-4M) protected the retina from the excitotoxicity according to ChAT IR, bNOS IR and TUNEL staining. Similar data were ob­tained in both animal species used. These results demonstrate for the first time the neuroprotective ac­tions of a somatostatin analog injected intravitreally and support the further study of the use of soma­tostatinergic analogs as therapeutics in retinopathies.