Retinal ganglion cell dysfunction in humans following post-geniculate lesions: specific spatio–temporal losses revealed by pattern ERG

Abstract

Nasal and temporal hemifield (14 x 24 degrees) pattern electroretinograms (PERGs) were recorded in eight patients (age range: 21-72 years) suffering from different post-geniculate lesions (documented by CT scan and/or MRI of the brain) and homonymous hemianopia at visual field testing. In total eight age-matched normal subjects served as controls. PERGs were elicited by alternating, sinusoidal gratings (90% contrast), whose spatial and temporal characteristics, 6 Hz-5 c deg-1 and 15 Hz-0.58 c deg-1, were chosen to enhance the relative contributions of parvo- (P) and magno- (M) retinal ganglion cell (GC) subsystems, respectively. Amplitudes and phases of the Fourier analyzed PERG 2nd harmonics were measured. In normal subjects, PERG amplitudes to 15 Hz-0.58 c deg-1, but not those of the 6 Hz-5 c deg-1 stimuli were on average larger (P < 0.05) in nasal than in temporal hemiretinae. In hemianopic patients, PERG amplitudes of 6 Hz-5 c deg-1 stimuli were on average reduced (P < 0.05) in the hemiretinae corresponding to blind hemifields, in comparison to those in the hemiretinae corresponding to functional hemifields. No differences between hemiretinae were observed for responses of the 15 Hz-0.58 c deg-1 stimuli. In both normal subjects and patients, average PERG phases did not differ between hemiretinae, while changing significantly (P < 0.01) across stimulus conditions. The PERG naso-temporal asymmetries observed in normal subjects are consistent with the reported asymmetries in GC density observed histologically (Curcio & Allen. (1990). Journal of Comparative Neurology, 300, 5-25). The results in patients indicate that the PERGs to specific spatio-temporal stimuli (i.e. of relatively low-temporal and high-spatial frequency), presented in the hemianopic field, are reduced in amplitude. This suggests, in agreement with the experimental findings in monkeys (Cowey & Stoerig. (1991). Trends in Neuroscience, 14, 140-145), that retrograde trans-synaptic dysfunction of P-GCs, with relative sparing of the M-subsystem, may occur in humans following lesions of post-geniculate pathways.

Trans‐synaptic axonal degeneration in the visual pathway in multiple sclerosis

“…10 However, we could not differentiate whether there was trans-synaptic retrograde degeneration within the OR. 2,[27][28][29][30][31] With new imaging approaches, it was found that MS patients who had suffered ON developed abnormalities in the OR (evident by diffusion tensor imaging and tractography) 11,13,14,32 or in the cortex (assessed by magnetic transference imaging or brain spectroscopy), 12,33 even some time after focal injury, indicative of trans-synaptic damage. Previous studies in animal models have demonstrated the existence of transsynaptic degeneration after focal brain damage, [23][24][25][26] revealing the potential spreading effect of focal WM lesions along WM tracts and through networks within the brain.…”

“…Such a phenomenon has also been studied in the human visual pathway after focal damage of a different nature in either the visual cortex or optic nerve, providing evidence of trans-synaptic degeneration between the anterior and posterior visual pathway. 2,[27][28][29][30][31] With new imaging approaches, it was found that MS patients who had suffered ON developed abnormalities in the OR (evident by diffusion tensor imaging and tractography) 11,13,14,32 or in the cortex (assessed by magnetic transference imaging or brain spectroscopy), 12,33 even some time after focal injury, indicative of trans-synaptic damage. Our study is consistent with these previous findings, entering into more detail by allowing retrograde and anterograde damage to be assessed.…”

Macular Ganglion Cell Layer and Peripapillary Retinal Nerve Fibre Layer Thickness in Patients with Unilateral Posterior Cerebral Artery Ischaemic Lesion: An Optical Coherence Tomography Study

“…18,19 New evidence rose to light with pattern-evoked electroretinogram studies in the 1990s that found differences in signal strength between the two hemiretinas of homonymous hemianopic patients. 20,21 More recently, resource to high-resolution magnetic resonance imaging revealed optic tract thinning in hemianopic patients. 22 The development of OCT technology allowed for an easy and non-invasive analysis of the retina and the optic disc.…”

Conclusive Evidence for Human Transneuronal Retrograde Degeneration in the Visual System

“…The first report of abnormal PERGs in a hemianopic patient was provided by Stoerig & Zrenner [16] who found differences both between the two hemiretinae of the patient and in comparison to a sighted control subject. This finding was strengthened by a larger study by Porrello & Falsini [17] of eight hemianopic patients (6 right hemisphere damages). They not only found a significant difference between affected and unaffected hemiretinae in the patients, but also that the loss in signal correlated with the time since the lesion.…”