A non‐canonical rhodopsin‐mediated insulin receptor signaling pathway in retinal photoreceptor neurons

Abstract

We previously reported a ligand‐independent and rhodopsin‐dependent insulin receptor (IR) neuroprotective signaling pathway in both rod and cone photoreceptor cells, which is activated through protein–protein interaction. Our previous studies were performed with either retina or isolated rod or cone outer segment preparations and the expression of IR signaling proteins were examined. The isolation of outer segments with large portions of the attached inner segments is a technical challenge. Optiprep™ density gradient medium has been used to isolate the cells and subcellular organelles, Optiprep™ is a non‐ionic iodixanol‐based medium with a density of 1.320 g/mL. We employed this method to examine the expression of IR and its signaling proteins, and activation of one of the downstream effectors of the IR in isolated photoreceptor cells. Identification of the signaling complexes will be helpful for therapeutic targeting in disease conditions.

Insulin-like growth factor-2 regulates basal retinal insulin receptor activity

“…Collectively, the data indicate that the retinal IR is activated by both ligand-dependent and ligand-independent, light-induced mechanisms. The latter is primarily related to photoreceptors ( 40 ), whereas the ligand-dependent activation is more likely acting on nonphotosensitive inner retinal cells.…”

Higher Aqueous Levels of Resistin and Lipocalin-2 Indicated Worse Visual Improvement following anti-VEGF Therapy in Patients with Retinal Vein Occlusion

“…Our results suggest that resistin may participate in the thrombotic process but may not be involved in vascular leakage (macular oedema) in CRVO. The metabolism of retinal neurons, in particular, photoreceptors are known to relay, at least partially on the insulin signaling pathway 39 . Whether higher intraocular level resistin in CRVO causes insulin resistance and impairs photoreceptor metabolism remains to be determined.…”

Signaling roles of phosphoinositides in the retina

“…The IR activation has been shown to be independent of G protein transducin activation and dependent on the photobleaching of rhodopsin ( 52 ). This IR/PI3K activation is a noncanonical rhodopsin activation ( 105 ) ( Fig. 4 ).…”

“…The IR/PI3K/Akt signaling proteins are also expressed in the rod inner segments. These proteins may play an important role in cellular signaling events ( 105 ). One of the functions of PI3K-activated Akt in the inner segment is to regulate hexokinase 2 as it interacts with mitochondria in the photoreceptors ( 125 ).…”