Opn4, also known as melanopsin, is a ubiquitously expressed photoreceptor in vertebrates. It is crucial for both visual and non-visual signaling, such as regulating circadian rhythms, supporting visual functions by sensing radiance levels and contrast, and controlling retinal growth and development processes. Opn4 can activate the canonical Gq pathway, as well as Gi heterotrimers, signaling through the G protein βγ [4].

In melanoma research, Opn4KO mice showed slower melanoma cell proliferation due to impaired cell cycle progression and reduced Mitf expression. In vivo, Opn4KO tumors had slower growth and higher immune response, indicating OPN4 as an oncogene in melanoma [1]. In murine melanocytes, Opn4KO cells had a faster cell cycle progression and growth rate, suggesting a potential tumor-suppression role in normal melanocytes [5]. In the study of myopia, Opn4-/-mice had altered normal refractive development and greater susceptibility to form-deprivation myopia, with changes in dopamine signaling [3]. Regarding skin, Opn4KO mice had histological and proteomic differences, and OPN4 was shown to play a protective role in skin physiology and attenuate UVA-induced damage [2].

In conclusion, Opn4 is essential for various biological functions including circadian rhythm regulation, visual and non-visual signaling, and cell-cycle regulation in melanocytes. The use of Opn4KO mouse models has revealed its significance in diseases such as melanoma, myopia, and skin-related conditions, providing insights into potential therapeutic targets for these diseases.

References:

1. de Assis, Leonardo Vinícius Monteiro, Lacerda, José Thalles, Moraes, Maria Nathália, Câmara, Niels Olsen Saraiva, Castrucci, Ana Maria de Lauro. 2022. Melanopsin (Opn4) is an oncogene in cutaneous melanoma. In Communications biology, 5, 461. doi:10.1038/s42003-022-03425-6. https://pubmed.ncbi.nlm.nih.gov/35562405/

2. Sua-Cespedes, Cristhian, Lacerda, José Thalles, Zanetti, Giovanna, de Assis, Leonardo V M, Castrucci, Ana Maria L. 2023. Melanopsin (OPN4) is a novel player in skin homeostasis and attenuates UVA-induced effects. In Journal of photochemistry and photobiology. B, Biology, 242, 112702. doi:10.1016/j.jphotobiol.2023.112702. https://pubmed.ncbi.nlm.nih.gov/37018912/

3. Chakraborty, Ranjay, Landis, Erica G, Mazade, Reece, Iuvone, P Michael, Pardue, Machelle T. 2021. Melanopsin modulates refractive development and myopia. In Experimental eye research, 214, 108866. doi:10.1016/j.exer.2021.108866. https://pubmed.ncbi.nlm.nih.gov/34838844/

4. Kankanamge, Dinesh, Ratnayake, Kasun, Samaradivakara, Saroopa, Karunarathne, Ajith. 2018. Melanopsin (Opn4) utilizes Gαi and Gβγ as major signal transducers. In Journal of cell science, 131, . doi:10.1242/jcs.212910. https://pubmed.ncbi.nlm.nih.gov/29712722/

5. de Assis, Leonardo Vinícius Monteiro, Moraes, Maria Nathália, Mendes, Davi, Menck, Carlos Frederico Martins, Castrucci, Ana Maria de Lauro. 2021. Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes. In Current issues in molecular biology, 43, 1436-1450. doi:10.3390/cimb43030101. https://pubmed.ncbi.nlm.nih.gov/34698095/