Serum neuronal, glial and mitochondrial markers in autosomal dominant optic atrophy and Leber hereditary optic neuropathy.

Leber hereditary optic neuropathy (LHON) and autosomal-dominant optic atrophy (ADOA) are the two most prevailing primary mitochondrial optic neuropathies. Both diseases preferentially affect the smallest retinal ganglion cells (GCs) of the papillomacular bundle, causing central visual loss in young patients. Although ADOA and LHON show striking similarities, including the convergence of underlying pathologic mitochondrial mechanisms, they differ clinically. The major distinction lies in the timing and progression of axonal damage during neurodegeneration. The exact reasons for these differences remain unclear, but they may, in part, be due to distinct patterns of mitochondrial dysfunction. To identify differences that could point to distinct degenerative processes, we investigated clinical features, optical coherence tomography (OCT) findings, laboratory biomarkers [serum neurofilaments light chain (sNfL), serum glial fibrillary acidic protein (sGFAP) and serum growth differentiation factor-15 (sGDF15)] in a cohort of patients with these two heritable optic neuropathies in the chronic phase. Our OCT analysis reveals a more profound GC layer and papillomacular bundle loss in LHON, whereas ADOA shows a sparser damage of the retinal nerve fibre layer, including fibres originating from the nasal retina. We also observed increased plasma levels of sNfL and GFAP in both groups, supporting the presence of ongoing neurodegeneration in both optic neuropathies. Finally, our findings suggest the retinal astrocytes may play a contributive role in the neurodegenerative process at the level of the optic nerve head, particularly in ADOA.