Overexpression of ROM-1 in the cone-dominant retina

ROM-1 (rod outer segment membrane protein-1) is a tetraspanin protein present in the outer segment (OS) rims of rod and cone photoreceptors. It shares many common features with other tetraspanins, including a large intradiscal loop which contains several cysteines. This loop enables ROM-1 to associate with its homologue retinal degeneration slow (RDS) to form hetero-tetramers and hetero-octamers. Although large RDS homo-oligomers are required for building and maintaining the rim region of rod discs and cone lamellae, the function of ROM-1 is less clear. ROM-1 is not necessary for disc morphogenesis but is required for fine tuning OS disc size and structure. Furthermore, the role of ROM-1 has not been well studied in cone photoreceptors. To help alleviate this knowledge gap, we overexpressed ROM-1 via transgenesis in the cone-dominant nrl ^-/- mouse retina. We show that ∼20% overexpression of ROM-1 results in vacuoles in the cone OSs and significant reductions in photopic electroretinogram responses. These results indicate that overexpression of ROM-1 is harmful to cone OSs. We hypothesize that overexpression of ROM-1 alters the normal balance between RDS homo-oligomers and RDS/ROM-1 heteromeric complexes, resulting in insufficient or abnormal higher-order RDS homo-oligomers for the maintenance of proper OS structure and function.