The Pattern of Retinal Ganglion Cell Loss in OPA1-Related Autosomal Dominant Optic Atrophy Inferred From Temporal, Spatial, and Chromatic Sensitivity Losses

Abstract

PurposeProgressive retinal ganglion cell (RGC) loss is the pathological hallmark of autosomal dominant optic atrophy (DOA) caused by pathogenic OPA1 mutations. The aim of this study was to conduct an in-depth psychophysical study of the visual losses in DOA and to infer any selective vulnerability of visual pathways subserved by different RGC subtypes.MethodsWe recruited 25 patients carrying pathogenic OPA1 mutations and age-matched healthy individuals. Spatial contrast sensitivity functions (SCSFs) and chromatic contrast sensitivity were quantified, the latter using the Cambridge Colour Test. In 11 patients, long (L) and short (S) wavelength–sensitive cone temporal acuities were measured as a function of target illuminance, and L-cone temporal contrast sensitivity (TCSF) as a function of temporal frequency.ResultsSpatial contrast sensitivity functions were abnormal, with the loss of sensitivity increasing with spatial frequency. Further, the highest L-cone temporal acuity fell on average by 10 Hz and the TCSFs by 0.66 log10 unit. Chromatic thresholds along the protan, deutan, and tritan axes were 8, 9, and 14 times higher than normal, respectively, with losses increasing with age and S-cone temporal acuity showing the most significant age-related decline.ConclusionsLosses of midget parvocellular, parasol magnocellular, and bistratified koniocellular RGCs could account for the losses of high spatial frequency sensitivity and protan and deutan sensitivities, high temporal frequency sensitivity, and S-cone temporal and tritan sensitivities, respectively. The S-cone–related losses showed a significant deterioration with increasing patient age and could therefore prove useful biomarkers of disease progression in DOA.

Differential susceptibility of retinal ganglion cell subtypes in acute and chronic models of injury and disease

“…Previous studies have used various injury and disease models in different animals to elucidate the loss of specific RGCs subtypes, with results somewhat variable based on the model system or the organism used [12][13][14][15][16][17][18][19][20] . Results of the current study demonstrated a high susceptibility for direction selective-RGCs and alpha-RGCs, with this phenomenon observed similarly in a number of other studies 22,23,25 .…”

Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells

“…In addition, blinding diseases which cause degeneration and eventual death of RGCs often appear to preferentially target one subtype over others ( Duan et al., 2015 , El-Danaf and Huberman, 2015 , Majander et al., 2017 , Ohlemacher et al., 2016 , Puyang et al., 2017 ). With the advancement of patient-specific hPSCs, RGC subtypes can be identified using molecular markers in disease models such as glaucoma, with an emphasis on whether one subtype is predominantly targeted for degenerative effects compared with other subtypes.…”

Quantitative physiological measurements to evaluate the response of antivascular endothelial growth factor treatment in patients with neovascular diseases

“…A lot of novel and unique physiological tests have been available recently, including functional OCT, chromatic contrast, investigating changes of preferred retinal location and vision-related quality of life. [ 92 93 94 95 ] However, this review has a limitation that we only included quantitative measurement methods, which we considered more accessible in general clinical settings. Nevertheless, our review proved that intravitreal injection of anti-VEGF agents appear safe and may offer a new therapeutic opportunity for neovascular diseases with a significant impact on visual function.…”