Kcnv2 encodes Kv8.2, a voltage-gated potassium channel subunit. It acts as a modulator by shifting the activation range of the K+ channels in photoreceptor inner segments, playing a crucial role in the normal function of the retina [1].

Mutations in Kcnv2 are associated with an autosomal recessive cone-rod dystrophy known as KCNV2-associated retinopathy or “cone dystrophy with supernormal rod responses”. Patients with this condition typically show decreased visual acuity, reduced color vision, photophobia, nyctalopia, and nystagmus. The disease progresses slowly, and legal blindness may be reached before the age of 25. Full-field electroretinograms (ERGs) show pathognomonic waveform features, such as a disproportionate increase in b-wave amplitude with a relatively small light intensity increase, delayed a-wave and b-wave peak times, and a higher than normal b:a wave ratio. Retinal imaging reveals features like bull's eye maculopathy pattern in fundus autofluorescence (FAF) and variable foveal disruption on optical coherence tomography (OCT) [1,2,3,4].

In conclusion, Kcnv2 is essential for the normal function of retinal photoreceptor inner segments. The study of KCNV2-associated retinopathy, often through clinical and genetic analysis of patients rather than traditional KO/CKO mouse models in the provided references, has provided insights into the disease mechanism. Understanding Kcnv2's role in this disease may help develop future therapeutic strategies for this currently untreatable condition [1].

References:

1. Guimaraes, Thales A C De, Georgiou, Michalis, Robson, Anthony G, Michaelides, Michel. 2020. KCNV2 retinopathy: clinical features, molecular genetics and directions for future therapy. In Ophthalmic genetics, 41, 208-215. doi:10.1080/13816810.2020.1766087. https://pubmed.ncbi.nlm.nih.gov/32441199/

2. Georgiou, Michalis, Robson, Anthony G, Fujinami, Kaoru, Héon, Elise, Michaelides, Michel. 2020. KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1. In American journal of ophthalmology, 225, 95-107. doi:10.1016/j.ajo.2020.11.022. https://pubmed.ncbi.nlm.nih.gov/33309813/

3. Sakti, Dhimas H, Cornish, Elisa E, Ali, Haipha, Jamieson, Robyn V, Grigg, John R. 2024. Natural history and biomarkers of KCNV2-associated retinopathy. In Clinical & experimental ophthalmology, 52, 528-544. doi:10.1111/ceo.14373. https://pubmed.ncbi.nlm.nih.gov/38443311/

4. Georgiou, Michalis, Fujinami, Kaoru, Vincent, Ajoy, Zrenner, Eberhart, Michaelides, Michel. 2021. KCNV2-Associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints-KCNV2 Study Group Report 2. In American journal of ophthalmology, 230, 1-11. doi:10.1016/j.ajo.2021.03.004. https://pubmed.ncbi.nlm.nih.gov/33737031/