A novel recurrent ARL3 variant c.209G > A p.(Gly70Glu) causes variable non-syndromic dominant retinal dystrophy with defective lipidated protein transport in human retinal stem cell models.

Inherited retinal dystrophies (IRDs) are characterized by their high clinical and genetic heterogeneity. Despite significant advances in the identification of genes associated with IRDs, many individuals and families still have not received a definite molecular diagnosis. Here, we performed clinical examinations and conducted genetic testing in five families with IRD.

Disruption of mitochondrial homeostasis and permeability transition pore opening in OPA1 iPSC-derived retinal ganglion cells.

Dominant optic atrophy (DOA) is the most common inherited optic neuropathy, characterised by the selective loss of retinal ganglion cells (RGCs). Over 60% of DOA cases are caused by pathogenic variants in the OPA1 gene, which encodes a dynamin-related GTPase protein. OPA1 plays a key role in the maintenance of the mitochondrial network, mitochondrial DNA integrity and bioenergetic function.

Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids.

Bialleleic pathogenic variants in LCA5 cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment. Here, we report the use of gene editing to generate isogenic LCA5 knock-out (LCA5 KO) induced pluripotent stem cells (iPSC) and their differentiation to retinal organoids. The molecular and cellular phenotype of the LCA5 KO retinal organoids was studied in detail and compared to isogenic controls as well as patient-derived retinal organoids.

Light as a Mediator of Acute and Chronic Retina Degeneration.

In age-related macula dystrophy (AMD) and some forms of inherited retinal dystrophies (IRDs), blindness is caused by the loss of photoreceptors and retinal pigment epithelium (RPE) cells. This process can be exacerbated by genetic and environmental risk factors, including exposure of the retina to bright light. Several light damage models have been developed and have proved to be powerful tools to study retinal degeneration.