Response of the Rat Eye to Acute and Chronic Optic Nerve Pressure Modifications

Purpose: This study examines whether the response of the rat optic nerve tissue to either acute or chronic intraocular pressure (IOP) elevation is affected when optic nerve sheath pressure is reduced via optic nerve sheath fenestration. Methods: In the acute study, Long Evans rats underwent optic nerve sheath fenestration and IOP elevation (10-80 millimeters of mercury [mm Hg]). Optic nerve tissue response was assessed using optical coherence tomography (OCT) at each IOP step and compared with naïve and sham operated eyes (n = 6/group). In the chronic study, three treatment groups (n = 10) were given a circumlimbal suture to induce ocular hypertension (OHT); the fenestration group (F + OHT group), the suture-only OHT group (OHT group), and the sham-fenestrated OHT group (SF + OHT group). Fenestration-only (n = 14) and age-matched naïve rats (n = 6) were also included. IOP was measured weekly, and OCT and electroretinography (ERG) were conducted at weeks 4 and 8 after surgery. After week 8, RBPMS stained cells were counted. Results: In the acute study, the fenestrated group showed greater posterior retinal surface deformation (P = 0.008) and retinal compression with IOP elevation (P = 0.009). In the chronic study, the F + OHT group showed greater retinal nerve fiber layer (RNFL) thinning (P = 0.009) and worse ganglion cell function (P < 0.0001) compared with the control groups. RBMPS staining showed greater retinal ganglion cell (RGC) loss in the fenestrated group compared to the naïve group (P = 0.007) but not the F + OHT group (P = 0.051). Conclusions: Low optic nerve sheath pressure via optic nerve sheath fenestration exaggerates biomechanical and functional impacts of IOP elevation. These data provide insight into the role of cerebrospinal fluid pressure in glaucoma pathogenesis.