Skip to main content
. 2023 Nov 8;108(4):495–505. doi: 10.1136/bjo-2022-323071

Figure 3.

Figure 3

Current and future treatment agents for STGD1 A schematic showing (A) current pharmacological STGD1 treatment agents and (B) novel genetic therapies for STGD1. (A) Schematic showing the normal visual cycle (pink) and failure of transport due to ABCA4 dysfunction (blue). Agents (RPE65 inhibitors, deuterated Vitamin A, RBP4 antagonists) lower the formation of toxic products of the retinoid cycle by enzymatic inhibition, reducing delivery of vitamin A, or antagonising the retinoid binding protein 4 (RBP4). (B) Schematic showing non-integrating episomal and integrating nuclear gene therapies. The ABCA4 gene is expressed in retinal photoreceptors and the transporter is localised at the rim of rod and cone photoreceptors at the outer segment (OS), which connects to the inner segment (IS) via connecting cilium (CC). To target disordered transport due to ABCA4 dysfunction, adeno-associated virus (AAV) therapies deliver the large 6.4 kb ABCA4 gene (>4.7 kb AAV cargo limit) to the nucleus by splicing together fragments of the ABCA4 gene, wherein the transgene remains in an episomal state. Gene editing therapies cut or alter single nucleotide(s) within the ABCA4 gene via techniques such as CRISPR-Cas, which targets specific variants. Gene coding replaces the entire ABCA4 gene via an engineered transposase, enabling its application to all variants, including exonic and intronic nucleotide variants, as well as structural variants.