Short and Long Term Effects of Chronic Ocular Hypertension on the Retinotectal Projection: Neuroprotective Effects of Two Hypotensive Drugs

Abstract

Abstract: : Purpose: To study the effects of chronic ocular hypertension on the retino–tectal innervation and the possible 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 (WoldeMussie et al., 2001; IOVS 42:2849). These eyes were treated twice daily with 5 µl of Alphagan–P, Timoptic or 0,9% NaCl. Intraocular pressure (IOP) was measured with a Tono–Pen prior to, and 1, 2, 5 and 9 weeks after lasering in the experimental rats and in an additional group of unlasered (naïve) rats. The neuroprotective effects of antiglaucomatous drugs were investigated by examining at 2 and 9 weeks retinal afferents to the superior colliculus (SC) anterogradely labeled with Cholera Toxin B subunit (CTB) applied to the eyes. Results: Laser treatment to episcleral and limbal veins results 2 w later in a two–fold increase of the IOP. Topical treatment with Alphagan–P– or Timoptic produced significant reductions of the IOP. At 19 or 68 d after lasering, the volume of the retino–tectal projection was 4.11±0.3 (n=14) or 4.09±0.31 (n=16), 3.32±0.47 (n=12) or 3.13±0.74 (n=13), 3.9±0.33 (n=11) or 3.78±0.8 (n=15), and 3.51±0.44 (n=14) or 3.19±0.63 (n=15), for the unlesioned, vehicle–, Alphagan–P–, and Timolol–treated groups of rats, respectively. There were significant reductions in the volume of the retino–tectal projections in the timolol– and vehicle–treated groups both a19 and 68 d after lasering. Conclusions: OHT results in the loss of approximately 19% or 23% of the retino–tectal terminals by 19 or 68 days after lasering. Timoptic treatment did not prevent retino–tectal degeneration, and Alphagan–P–treatement resulted in loss of 5% or 7%, thus providing a statistically significant protection against OHT–induced degeneration of the retinotectal projection. Both Alphagan–P and Timoptic were effective to diminish laser–induced IOP, but only Alphagan–P protected against COHT–induced degeneration of retino–tectal terminals. These results are consistent with previous studies (WoldeMussie et al., 2001, IOVS 42:2849; 2004, GLIA 47:109), showing a similar degree of protection against OHT–induced retinal ganglion cell death.

Keywords: neuroprotection • retina • intraocular pressure