# Alterations of Photoreceptor Synaptic Ribbons in the Retina of a Human Patient With Oculocutaneous Albinism Type 1 (OCA1)

## TL;DR

This study shows that a human patient with OCA1 has abnormal photoreceptor synaptic ribbons, similar to albinotic mice, due to melanin deficiency, not genetic mutations in the RIBEYE gene.

## Contribution

The study demonstrates that OCA1 causes synaptic ribbon defects in human retinas, similar to mouse models, but not due to RIBEYE gene mutations.

## Key findings

- OCA1 patient's photoreceptor synaptic ribbons were abnormally small and fragmented.
- RIBEYE gene in the OCA1 patient had no mutations, only SNPs also found in controls.
- Synaptic ribbon defects in OCA1 are likely indirect effects of melanin biosynthesis deficiency.

## Abstract

Albino (Tyrc-2J/Tyrc-2J) C57BL/6J mice carry a mutation in the tyrosinase gene and are known to display alterations of photoreceptor synaptic ribbons. In the present study, we wanted to test whether similar alterations exist in oculocutaneous albinism type 1 (OCA1), a human disease that also results from mutations in the tyrosinase gene.

In the present study, we assessed the morphology of a human OCA1 retina in comparison to control human retinas. We analyzed the retina of a 35-year-old OCA1 patient by immunolabeling at light and electron microscopic levels, conventional transmission electron microscopy, and by genomic DNA sequencing of the RIBEYE/CtBP2 gene in comparison to normal human controls.

The morphological analyses revealed an overall surprisingly normal appearance of the retina, except for the presence of strikingly abnormal photoreceptor synaptic ribbons. Synaptic ribbons are presynaptic specializations of the continuously active retinal ribbon synapses and mainly consist of the RIBEYE protein. In the OCA1 patient, photoreceptor synaptic ribbons were very small and reduced to small fragments that were either still associated with the active zone transmitter release site or floating in the cytosol. The RIBEYE gene appeared to be unaltered in the OCA1 patient, except for some single nucleotide polymorphisms (SNPs) that were also present in controls.

The OCA1 patients displayed similar defects of photoreceptor synaptic ribbons as previously observed in the albinotic mice with a defect in the tyrosinase gene. The observed alterations of synaptic ribbons are not due to mutations in the RIBEYE gene but are likely indirect consequences of the deficient melanin biosynthesis in the OCA1 patient.