Photoreceptor Manifestations of Primary Mitochondrial Optic Nerve Disorders

Abstract

Purpose To compare the manifestations of photoreceptors (PRs) in three hereditary optic neuropathies affected by primary mitochondrial dysfunction and discuss whether the retinal ganglion cells (RGCs) or the PRs are preferentially affected. Methods A retrospective analysis of patients with genetically confirmed diagnoses of optic neuropathies associated with mitochondrial dysfunction was performed. This cohort included Leber's hereditary optic neuropathy (LHON), autosomal dominant optic atrophy type 1 (OPA1), and optic atrophy type 13 (OPA13). Patient chart evaluations included clinical characteristics, best-corrected visual acuity (BCVA), fundus photography, spectral-domain optical coherence tomography (SD-OCT), electroretinogram (ERG), and visual evoked potential data. Results This analysis included seven patients with LHON, six with OPA1, and one with OPA13 from a tertiary medical center. Thirteen of the 14 individuals were male. The average BCVA at diagnosis was 20/285 and 20/500 in the right and left eyes, respectively. Five of the seven patients with LHON, and three of the six patients with OPA1 also showed a mild amplitude reduction or delayed latency on light-adapted ERG and 30-Hz flicker responses; however, SD-OCT imaging did not show correlated PR abnormalities. Notably, a 7-year follow-up of a patient with OPA13 revealed degeneration of RGCs prior to the degeneration of PRs. Follow-up data also demonstrated continuous loss of cone outer segment tips on SD-OCT imaging. Conclusions RGCs are, in general, affected by mitochondrial dysfunction, whereas variable PR dysfunction exists in patients with LHON and OPA1, especially with respect to the cone responses. Involvement of PRs is particularly evident in OPA13 after RGC degenerations.

Maternal mosaicism in SSBP1 causing optic atrophy with retinal degeneration: implications for genetic counseling

“…1 B). Electrophysiological tests showed early optic nerve dysfunction followed by gradual loss of photoreceptor response as described in our previous study [ 8 ]. When the patient repeated exams by age 27, mid-peripheral retinal pigmentary changes appeared on fundus color photography and autofluorescence imaging (Fig.…”

“…Wide variability in phenotypes has been noticed in OPA13, and the SSBP1 genotype–phenotype correlations is not well-established yet. Among 60 published patients with missense SSBP1 variants, optic atrophy was present in 95% of them [ 4 – 8 ]. Sixty-five percent of patients had pigmentary changes on fundus photography, 57.8% presented with foveopathy on macular OCT, and 29.3% exhibited rod-cone degeneration on full-field ERG.…”

“…The SSBP1 gene was functionally characterized in 2019 and several families with OPA13 have been reported recently [ 4 , 6 , 7 ]. SSBP1 mutations could impair replication machinery in retinal ganglion cells (RGCs) and numerous other cell types [ 8 ]. Although OPA13 has been recognized as an autosomal dominant disorder [ 4 – 7 , 9 ], the SSBP1 genotype–phenotype correlations are not well understood.…”

“…In our previous work, a 16-year-old Taiwanese male with bilateral disc pallor, retinal vessel attenuation carried an SSBP1 variantc.320G>A (p.Arg107Gln) identified by whole exome sequence (WES) [ 8 ]. Here, we further discovered that the proband’s disease-causing variant was inherited from his unaffected mother, strongly indicating the maternal gonosomal mosaicism contributing to OPA13.…”

Attention-Deficit/Hyperactivity Disorder Animal Model Presents Retinal Alterations and Methylphenidate Has a Differential Effect in ADHD versus Control Conditions

“…Similarly, we observed that the ADHD model presents visual function impairment, with a deficit in the photoreceptors/bipolar cell circuits, and RGCs circuits. Thus, the impairment in these circuits demonstrates that the ADHD model has retinal function impairment that may be related to ADHD features, namely: distractibility and inattention [ 46 ] and reduced visual acuity [ 48 ], which are also described in ADHD children and adolescents [ 49 , 50 ]. However, we did not detect any alterations in the photopic b-wave in the ADHD conditions, which suggests that the bipolar cell’s function impairment is less subtle when the retina is light-adapted.…”