How the retina fine-tunes brightness
Researchers in the Department of Biological Sciences at KAIST have published a report describing the identification of a protein complex related to vision and an important biological role that it carries out. The work involves a study of a combination of three proteins that together can bind DNA. Once bound, this complex disallows the formation of a certain isoform Pax6 (also known as Pax6ΔPD). The study which involved mouse models involves data for Pax6ΔPD supporting that it is important for the specifying a group of amacrine cells. These cells release GABA neurotransmitter and, in turn desensitize the retina following a visual stimulus.
The retina is a sensory tissue that collects light and color information of objects and converts into electrical signals, which are then sent to the brain. After light detection by the photoreceptors in the retina, the first step in visual processing occurs in retinal interneurons that are either stimulated or inhibited by photoreceptors during the transmission of the light information to retinal ganglion cells wired to the brain. Changes in the composition and connectivity of these retinal interneurons, therefore, alter the output of the retina, modifying the visual information sent to the brain.
Neurons comprising the retina are produced before animals open their eyes for the first time. This process is regulated by various transcription factors, which bind specific DNA sequences and induce the expression of target genes that define the features of each cell type. Paired-homeobox 6 (PAX6) is an important transcription factor of retinal interneurons named as amacrine cells that tune the activity of bipolar cells, which receive light information collected by the photoreceptors and deliver it to retinal ganglion cells. The PAX6 expression is also regulated by other transcription factors that bind specific DNA sequences named ‘enhancers’ of PAX6 gene. The ‘α-enhancer’ is bound by various transcription factors that regulate PAX6 expression in neural progenitor cells in the embryonic retina and subsets of amacrine cells in the mature retina. However, the mechanism and physiological roles of α-enhancer-dependent PAX6 expression have remained unknown.
Recently, researchers at KAIST in the Department of Biological Sciences have identified a protein complex composed of (i) transforming growth factor ß1-induced transcript 1 protein (Tgfb1i1) and (ii) its partner transcription factors Lhx3 and (iii) Isl1 that bind DNA sequences in the α-enhancer to suppress the production of an isoform of Pax6, i.e., Pax6ΔPD. The authors, Kim et al., found that the Pax6ΔPD is important for the specifying a group of amacrine cells, which release GABA neurotransmitter and desensitize the retina following a visual stimulus. The mice deleted with Tgfb1i1 gene express higher amount of Pax6ΔPD to produce additional GABAergic amacrine cells in their retina, and consequently show a sustained light response. Conversely, the mice carry the auto-stimulation-defective ΔPBS mutation (Pax6ΔPBS ΔPBS) have reduced amount of Pax6ΔPD in the retina and becomes less sensitive to light. By analogy, Tgfb1i1-deficient mice are comparable to a person who is too sensitive to a light stimulus and who is dazzled even by normal daylight, while Pax6ΔPBS mice are comparable to a person who has difficulty in detecting weak light stimuli and fails to detect the objects under moonlight.
Collectively, this study proposes that personal variance of visual sensitivity and adaptation might be related, at least in part, with the composition of retinal neurons, of which numbers are determined by transcription factors targeting the α-enhancer.
“The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity” Yeha Kim, Soyeon Lim, Taejeong Ha, You-Hyang Song, Young-In Sohn, Dae-Jin Park, Sun-Sook Paik, Joo-Ri Kim-Kaneyama, Mi-Ryoung Song, Amanda Leung, Edward M Levine, In-Beom Kim, Yong Sook Goo, Seung-Hee Lee, Kyung Hwa Kang, Jin Woo Kim Elife 2017 Jan 31;6. Epub 2017 Jan 31.