In 2008, the Provencio lab was able to specifically destroy melanopsin cells in the fully developed mouse retina using an immunotoxin made of an anti-melanopsin antibody conjugated to the protein saporin. This resulted in lowered responsiveness to light/dark cycles; a similar characteristic was observed in gene-knockout mutants lacking rods, cones or melanopsin. Furthermore, light-induced negative masking, mediated by rods, cones and/or melanopsin cells, was missing in the mice lacking melanopsin cells. Therefore, Provencio suggested that cells containing melanopsin might be required to transmit rod and/or cone information for certain non-image forming visual responses.

In a 2006 study, Provencio explored the role of the protein RPE65 for photoentrainment. RPE65 is an important protein found in intrinsically photosensitive retinal ganglion cells (ipRGCs) that is necessary for regeneration of visual chromophore in rods and cones. RPE65 knockout mice (Rpe65(-/-)) showed much weaker phase shifts when compared to rodless, coneless mice, which suggested that RPE65 might have other roles.

In 1998, Provencio discovered melanopsin as a novel opsin in the photosensitive skin melanophores of the African clawed frog. In 2000, he showed that melanopsin is also present in mouse, rhesus macaques, and humans, where it is only present in the eye. The unique inner retinal localization of melanopsin indicated that melanopsin was not involved in image formation. Later, he demonstrated that the melanopsin pigment might be involved in entrainment of a circadian oscillator to light cycles in mammals.

Provencio was born in Bitburg, Germany and attended Lebanon Catholic High School in Lebanon, PA. During his undergraduate career at Swarthmore College, Provencio became interested in neuroscience while studying crayfish, cockroaches, and fireflies under Jon Copeland. From 1987 to 1989 he worked as a lab technician in Steve Reppert’s research laboratory at Massachusetts General Hospital, where he was introduced to the field of circadian biology. He graduated in 1987 from Swarthmore College with a B.A. in Biology and went on to earn his Ph.D. from the University of Virginia, a university with a strong network of circadian biologists, in 1996. During his postdoctoral training at Uniformed Services University, Provencio held assistant and associate professorships at Uniformed Services University, Department of Anatomy, Physiology, and Genetics where he still maintains an adjunct associate professorship. He is now a full Professor at the University of Virginia.

Ignacio Provencio (born 29 June 1965) is an American neuroscientist and the discoverer of melanopsin, a photopigment found in specialized photosensitive ganglion cells of the mammalian retina. Provencio served as the program committee chair of the Society for Research on Biological Rhythms from 2008 to 2010.