Objective: Mitochondrial 13513G>A mutation presenting as isolated Leber's hereditary optic neuropathy (LHON) without any extraocular pathology has not been reported in literature. We herein evaluate the clinical characteristics and heteroplasmy of m.13513G>A mutation manifesting as isolated LHON.Methods: Seven members of a Chinese family were enrolled in this study. All subjects underwent detailed systemic and ophthalmic examinations. Mitochondrial DNA in their blood was assessed by targeted PCR amplifications, next generation sequencing (NGS), and pyrosequencing. One hundred of blood samples from ethnic-matched healthy volunteers were tested by NGS and pyrosequencing as normal controls.Results: Isolated LHON without any other ocular or extraocular pathology was identified in a 16 year old patient in this family. Heteroplasmic m.13513G>A mutation was detected by NGS of the full mtDNA genome in the patient with mutant load of 33.56%, and of 26% 3 months and 3 years after the onset of LHON, respectively. No m.13513G>A mutation was detected in all his relatives by NGS. Pyrosequencing revealed the mutant load of m.13513G>A mutation of the LHON patient, his mother, father and sister were 22.4, 1.9, 0, and 0%, respectively. None of 100 healthy control subjects was detected to harbor m.13513G>A mutation either by NGS or by pyrosequencing of the full mt DNA genome.Conclusions: We first report m.13513G>A mutation with low mutant load presenting as isolated LHON. NGS of the full mitochondrial DNA genome is highly recommended for LHON suspects when targeted PCR amplification for main primary point mutations of LHON was negative.

Uveal melanoma is the most frequent primary intraocular cancer in adulthood and is mostly localised to the choroid. It can be treated using radiation therapy, laser therapy, local resection and enucleation, with the best results achieved by combining these procedures. However, up to half of patients develop metastatic disease. There are no efficacious treatment methods for patients in advanced stage or with metastasis. In recent years, several novel treatment modalities aimed at improving tumour control and reducing adverse events have emerged. This review summarises current clinical treatment methods and new therapeutic perspectives for uveal melanoma.

Background: To identify and investigate the effects of a novel splicing variant, c.1444-2A>C of OPA1, on its transcript, translation, and mitochondrial function, which was found in an 8-year-old patient with dominantly inherited optic atrophy (DOA). Materials and Methods: The clinical evaluations were performed at the Eye Center. Lymphoblast cell lines were generated from the patient, mother, and a normal control with the same haplotype of mitochondrial genome. The novel variant was confirmed by Sanger sequencing. The splicing alteration of cDNA was checked by both Sanger sequencing and agarose gel. OPA1 expression was carried out by RT-PCR and Western blotting. Transmission electron microscopy was used for mitochondrial morphology. Mitochondrial functions, including the rates of oxygen consumption, ATP generation, ROS product and membrane potential were assayed in lymphoblast cells. Results: The novel OPA1 splicing variant, c.1444-2A>C, led to a deletion of the 15th exon in mRNA transcript. Approximately 50% reduction of mRNA and protein expression was present in mutant cells as compared with controls. No marked depletion of mtDNA nor mitochondrial mass was caused by the splicing variant. However, defects that the impaired capacity of OXPHOS, reduced ATP generation, increased ROS and decreased membrane potential were observed in the mutant cells, which promoted a ubiquitin-binding mitophagy instead of apoptosis. Conclusions: The novel splicing variant, c.1444-2A>C resulted in OPA1 haploinsufficiency effect on its expression and mitochondrial function without mtDNA depletion. Our findings may provide new insights into the understanding of pathophysiology of DOA.