Abstract
Background: To induce a moderate chronic ocular hypertension (OHT) by injecting polidocanol, a foamed sclerosant drug, in the aqueous humor outflow pathway. Methods: Intraocular pressure (IOP) was monitored for up to 6 months. Pattern and full-field electroretinogram (PERG and ERG) were recorded and retinal ganglion cells (RGC) and retinal nerve fiber layer (RNFL) thickness were assessed in vivo with optical coherence tomography (OCT) and ex vivo using Brn3a immunohistochemistry. Results: In the first 3 weeks post-injection, a significant IOP elevation was observed in the treated eyes (18.47 ± 3.36 mmHg) when compared with the control fellow eyes (12.52 ± 2.84 mmHg) (p < 0.05). At 8 weeks, 65% (11/17) of intervention eyes had developed an IOP increase >25% over the baseline. PERG responses were seen to be significantly reduced in the hypertensive eyes (2.25 ± 0.24 µV) compared to control eyes (1.44 ± 0.19 µV) (p < 0.01) at week 3, whereas the ERG components (photoreceptor a-wave and bipolar cell b-wave) remained unaltered. By week 24, RNFL thinning and cell loss in the ganglion cell layer was first detected (2/13, 15.3%) as assessed by OCT and light microscopy. Conclusions: This novel OHT rat model, with moderate levels of chronically elevated IOP, and abnormal PERG shows selective functional impairment of RGC.
Highlights
Glaucoma is a major cause of irreversible blindness worldwide and is characterized by progressive optic nerve and retinal ganglion cells (RGC) degeneration [1]
We describe a method of inducing a moderate and persistent elevated Intraocular pressure (IOP) by injecting polidocanol, a foamed sclerosant drug, in the aqueous humor outflow pathway in order to overcome the drawbacks of the other experimental techniques previously mentioned
At both week 2 and week 12, we did not observe any significant reduction in retinal nerve fiber layer (RNFL) + ganglion cell layer (GCL) + IPL thickness (73.13 ± 3.46 μm) in the hypertensive eyes compared to the control eyes (74.52 ± 0.62 μm)
Summary
Glaucoma is a major cause of irreversible blindness worldwide and is characterized by progressive optic nerve and retinal ganglion cells (RGC) degeneration [1]. We describe a method of inducing a moderate and persistent elevated IOP by injecting polidocanol, a foamed sclerosant drug, in the aqueous humor outflow pathway in order to overcome the drawbacks of the other experimental techniques previously mentioned. We functionally evaluated this model for its selectivity in impairing RGCs by examining the retinal function of RGCs and photoreceptor-mediated responses using the pattern and full-field electroretinogram (PERG and ERG). We evaluated retinal nerve fiber layer (RNFL) thickness by using the spectral-domain optical coherence tomography (OCT) and counted the total population of RGCs using Brn3a immunohistochemistry
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