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

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.