Purpose:
To determine the functional and anatomic characteristics of variable retinal ganglion cell (RGC) loss in experimental glaucoma (ExGl).
Methods:
ExGl was induced in the right eyes of 5 rhesus monkeys by laser trabecular destruction (LTD). The duration of intraocular pressure elevation above 25 mmHg varied from 393 days to 407 days. The mean intraocular pressure (IOP) in the treated eyes varied from 35 ± 9 to 48 ± 11 mmHg. Each animal underwent multifocal electroretinographic (mfERG) testing on 5 to 7 occasions prior to LTD and 9 to 11 times following IOP elevation. A reversing ophthalmoscope was used to align the visual axis of the eyes with a stimulus monitor displaying 241 unstretched hexagonal elements. 215-1 m-sequence was employed with a frame rate of 75 Hz. Analysis included K1 RMS signal-to-noise determination for each of the central 6 rings. The signal epoch was taken as 10-to-180 ms and the noise from 700-to-870 ms of the low pass filtered response waveform. Comparisons were made between right eyes before and after IOP elevation and between right and left eyes after IOP elevation. 15 to 20 minutes prior to sacrifice, the IOP in the right eyes was manometrically set at 35 mmHg and 10 million 15 µm fluorescent microspheres were injected into the left ventricle. The eyes were enucleated and fixed in 4% paraformaldehyde. Optic nerve segments were post-fixed in osmium tetroxide and stained with paraphenylene diamine (PPD).
Results:
Despite the similar IOP profiles for the 5 animals, there was marked inconsistency in the number of surviving RGC axons. The percentage loss varied from nearly 100% to less than 5%. Even so, we observed the expected supranormal mfERG K1 responses to approximately the same amplitude in all of the right eyes. There was no obvious correlation of mfERG signal strength with RGC loss. Furthermore, the relative increase in signal RMS (compared to either the fellow eye or the same eye pre- and post-IOP elevation) was similar for all of the 6 rings. Likewise, choroidal blood flow as determined by total microsphere count, was similar in all 5 right eyes.
Conclusions:
In this sample of eyes with ExGl, the marked variability in RGC loss cannot be explained on the basis of differences in IOP profile, mfERG responses or choroidal blood flow. As such, this model of ExGl is similar to human chronic glaucoma, in which there can be considerable differences in individual susceptibility to IOP.
Keywords: ganglion cells • electrophysiology: non-clinical • blood supply