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LASER–INDUCED CHRONIC OCULAR HYPERTENSION RESULTS IN DEGENERATION OF RETINO–TECTAL AFFERENTS: NEUROPROTECTION WITH TOPICAL BRIMONIDINE.

¹ Oftalmologia, Universidad de Murcia, Murcia, Spain
² Biological Sciences, Allergan Inc., Irvine, CA

Commercial Relationships: S. Mayor–Torroglosa, None; E. WoldeMussie, Allergan Inc. E; G. Ruiz, Allergan Inc. E; A. García–Avilés, None; J.M. Bernal, None; L.A. Wheeler, Allergan Inc. E; M. Vidal–Sanz, Allergan Inc. F.

Grant Identification: PI82/00540/FS/01, BFI2002–03742, Allergan Inc.

Abstract

Purpose: To study the effects of chronic ocular hypertension on retino–tectal afferents, and the neuroprotective effects of topically applied Alphagan–P ®, Timoptic ® or saline.

Methods: In adult male Wistar rats (350–450 g), ocular hypertension (OHT) was induced in the right eye by laser photocoagulation of episcleral veins following already described techniques (WoldeMussie et al., 2001; IOVS 42:2849). Right after first laser treatment, the right eyes were treated topically twice daily with 5 µl of Alphagan–P, Timoptic or 0,9% NaCl. Intraocular pressure was measured with a tonopen prior to, 7 and 14 days after lasering in experimental and an additional group of unlesioned (naïve) animals. Retino–tectal afferents were identified with the orthogradely transported tracer cholera toxin subunit B (CTB), injected 5 days prior to sacrifice, in the vitreous of the right eye of experimental and naïve animls. Serial coronal sections (40 µm thick) of the midbrain were inmuno–stained for CTB. The visual layers of the contralateral superior colliculus (SC) were examined with the aid of an image analysis system, to estimate the volume of the retino–tectal projection.

Results: Photocoagulation of episcleral and limbal veins results two weeks later in twofold increased intraocular pressure (IOP) in the saline–treated group of animals (32.4±1.5; n=7) as compared to the naïve group of animals (15.5±0.6; n=8). Both Alphagan–P and Timoptic were similarly effective in diminishing the rise of IOP after laser treatment. Laser–induced OHT in the Alphagan–P– or Timpoptic–treated groups of animals was smaller than that of the saline–treated group of animals (p<0.05) and greater than that of the unlesioned naïve group of animals (p<0.05). The volume of the retino–tectal projection was 4.10±0.39 (n=8), 3.56±0.23 (n=7), 3.56±0.51 (n=8), or 3.87±0.34 (n=7), for the naïve, saline–, Alphagan–P–, or Timolol–treated groups of rats, respectively.

Conclusions: OHT induces within three weeks the loss of approximately 13% of the retino–tectal terminals, Timoptic treatment did not prevent retino–tectal degeneration, and Alphagan–P–treatement provided a statistically significant protection against OHT–induced degeneration of the retinotectal projection.

Keywords: neuroprotection • ganglion cells • intraocular pressure

© 2004, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo{at}arvo.org.