Effects of optic nerve crush and ocular hypertension on the reflectance spectrum and cytostructure of the retinal nerve fiber layer of rats

Abstract

Purpose : Animal models of optic nerve crush (ONC) and ocular hypertension (OHT) are commonly used to study axonal degeneration. Both models lead to retinal ganglion cell (RGC) death. The details of RGC injury, however, are different. This study reports the effects of ONC and OHT on the optical properties and cytostructure of the retinal nerve fiber layer (RNFL).

Methods : ONC or OHT was induced in one eye of each Wistar rat. The contralateral eye was untreated. Both retinas of an animal were studied at one to four weeks after ONC or OHT treatment. The reflectance spectra (S_refl) of RNFL were measured at 400 – 830 nm and normalized for comparison. S_refl of normal RNFL was obtained from previous studies. Axonal cytoskeleton, F-actin, microtubules (MTs) and neurofilaments (NFs), were evaluated with confocal microscopy.

Results : Twelve rats with ONC and 14 rats with OHT were studied. Both models produced changes in the cytoskeleton and S_refl of the RNFL. In the ONC groups, all treated retinas showed distortion of axonal F-actin across the retina and the severity of distortion increased with survival days after ONC. Distortion of MTs and NFs occurred later than F-actin. The S_refl of ONC eyes was either nearly normal or changed at short wavelengths (Fig. C). In the OHT groups, cytoskeletal distortion was also found in all treated eyes. The distortion, however, was sectorial with the severity of distortion varying within the same retinas. Change of the S_refl of OHT eyes occurred either at short wavelengths only (Fig. F) or at all wavelengths. Major differences were as follows: 1) in ONC rats the untreated contralateral eyes also showed F-actin distortion while in OHT rats they showed no apparent structural change (Fig. B and E), 2) the S_refl of the untreated eyes in ONC rats may change while the S_refl of the untreated eyes in the OHT rats was similar to the normal (Fig. C and F), and 3) in ONC rats change of S_refl was similar along bundles while in OHT rats change of S_refl was different along bundles, with change more prominent near the optic nerve head.

Conclusions : Untreated contralateral eyes in the ONC model cannot be used as controls to study RNFL optical properties. The mechanisms underlying change of RNFL reflectance may be different in the ONC and OHT models.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.