Reversal of functional loss in a rat model of chronic intraocular pressure elevation

Abstract

Purpose: This pilot study considered whether intraocular pressure (IOP) lowering could reverse ganglion cell dysfunction in a rat model of chronic ocular hypertension. Methods: A circumlimbal suture was applied in one eye to induce ocular hypertension (n = 7) in Long-Evans rats. The contralateral eye served as an untreated control. After 8 weeks of IOP elevation the suture was removed to lower IOP for the remaining 7 weeks. Electroretinogram (ERG) and optical coherence tomography (OCT) were measured at baseline, 2, 4, 8, 12 and 15 weeks. Retinae were collected for histology at week 15. Results: In sutured eyes, IOP was elevated by 7–11 mmHg above control eyes (12 ± 0.2 mmHg [standard error of the mean]). Eight weeks of chronic IOP elevation resulted in a reduction of the ganglion cell mediated positive Scotopic Threshold Response (pSTR, −25 ± 7% of baseline), as well as smaller photoreceptor (−7 ± 4%) and bipolar cell mediated responses (−6 ± 5%). After suture removal, IOP recovered to normal. By 15 weeks the a-wave (0 ± 6%), b-wave (−2 ± 6%) and pSTR had recovered back to baseline (from −25 ± 7% to −4 ± 6%). The retinal nerve fiber layer was thinned by −9 ± 3% at week 8 and showed no further decline at week 15 (−10 ± 2%). Cell numbers in the ganglion cell layer were similar between suture removal and control eyes at week 15 (3543 ± 478 vs 4057 ± 476 cells mm−2). Conclusions: The circumlimbal suture model might be a useful platform to study the reversibility of neuronal dysfunction from chronic IOP challenge.