Last update 01 Nov 2024

LRIT3

Last update 01 Nov 2024

Basic Info

Synonyms

CSNB1F, FIGLER4, FLJ44691

+ [3]

Introduction

Plays a role in the synapse formation and synaptic transmission between cone photoreceptor cells and retinal bipolar cells (By similarity). Required for normal transmission of a light-evoked stimulus from the cone photoreceptor cells to the ON-bipolar cells and ON-ganglion cells in the inner retina (PubMed:28334377). Required in retinal ON-bipolar cells for normal localization of the cation channel TRPM1 at dendrite tips (By similarity). Seems to play a specific role in synaptic contacts made by ON-bipolar cells with cone photoreceptor pedicles (By similarity). May also have a role in cone synapse formation (By similarity). Might facilitate FGFR1 exit from the endoplasmic reticulum to the Golgi (PubMed:22673519). Could be a regulator of the FGFRs (PubMed:22673519).

Drugs associated with LRIT3

WO2022123282

Patent Mining

Target

LRIT3

Mechanism-

Active Org.

Centre National de la Recherche Scientifique [+1]

Originator Org.

Centre National de la Recherche Scientifique [+2]

Active Indication

Nervous System Diseases

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with LRIT3

100 Translational Medicine associated with LRIT3

0 Patents (Medical) associated with LRIT3

Literatures (Medical) associated with LRIT3

09 Sep 2024·Investigative Ophthalmology & Visual Science

Loss of ON-Pathway Function in Mice Lacking Lrit3 Decreases Recovery From Lens-Induced Myopia

Article

Author: Zhang, Jingyi ; Audo, Isabelle ; Zeitz, Christina ; Picaud, Serge ; Callebert, Jacques ; Wilmet, Baptiste ; Sahel, José Alain ; Michiels, Christelle

PurposeTo determine whether the Lrit3-/- mouse model of complete congenital stationary night blindness with an ON-pathway defect harbors myopic features and whether the genetic defect influences the recovery from lens-induced myopia.MethodsRetinal levels of dopamine (DA) and 3,4 dihydroxyphenylacetic acid (DOPAC) from adult isolated Lrit3-/- retinas were quantified using ultra performance liquid chromatography after light adaptation. Natural refractive development of Lrit3-/- mice was measured from three weeks to nine weeks of age using an infrared photorefractometer. Susceptibility to myopia induction was assessed using a lens-induced myopia protocol with -25 D lenses placed in front of the right eye of the animals for three weeks; the mean interocular shift was measured with an infrared photorefractometer after two and three weeks of goggling and after one and two weeks after removal of goggles.ResultsCompared to wild-type littermates (Lrit3+/+), both DA and DOPAC were drastically reduced in Lrit3-/- retinas. Natural refractive development was normal but Lrit3-/- mice showed a higher myopic shift and a lower ability to recover from induced myopia.ConclusionsOur data consolidate the link between ON pathway defect altered dopaminergic signaling and myopia. We document for the first time the role of ON pathway on the recovery from myopia induction.

01 Mar 2024·eneuro

Cone Synaptic Function is Modulated by the Leucine-Rich Repeat Adhesion Molecule LRFN2

Article

Author: Gregg, Ronald G ; Hasan, Nazarul

Daylight vision is mediated by cone photoreceptors in vertebrates, which synapse with bipolar cells (BCs) and horizontal (HCs) cells. This cone synapse is functionally and anatomically complex, connecting to eight types of depolarizing BCs (DBCs) and five types of hyperpolarizing BCs (HBCs) in mice. The dendrites of DBCs and HCs cells make invaginating ribbon synapses with the cone axon terminal, while HBCs form flat synapses with the cone pedicles. The molecular architecture that underpins this organization is relatively poorly understood. To identify new proteins involved in synapse formation and function we used an unbiased proteomic approach and identified LRFN2 (leucine-rich repeat and fibronectin III domain-containing 2) as a component of the DBC signaling complex. LRFN2 is selectively expressed at cone terminals and colocalizes with PNA, and other DBC signalplex members. In LRFN2 deficient mice, the synaptic markers: LRIT3, ELFN2, mGluR6, TRPM1 and GPR179 are properly localized. Similarly, LRFN2 expression and localization is not dependent on these synaptic proteins. In the absence of LRFN2 the cone-mediated photopic electroretinogram b-wave amplitude is reduced at the brightest flash intensities. These data demonstrate that LRFN2 absence compromises normal synaptic transmission between cones and cone DBCs.

01 Aug 2023·Vision Research

Extended functional rescue following AAV gene therapy in a canine model of LRIT3-congenital stationary night blindness

Article

Author: Aguirre, Gustavo D ; Kwok, Jennifer C ; Sato, Yu ; Takahashi, Kei ; Miyadera, Keiko

Congenital stationary night blindness (CSNB) is a group of inherited retinal diseases in which either rod-to-ON-bipolar cell (ON-BC) signaling, or rod function is affected leading to impaired vision under low light conditions. One type of CSNB is associated with defects in genes (NYX, GRM6, TRPM1, GPR179, and LRIT3) involved in the mGluR6 signaling cascade at the ON-BC dendritic tips. We have previously characterized a canine model of LRIT3-CSNB and demonstrated short-term safety and efficacy of an ON-BC targeting AAV-LRIT3 (AAV^K9#4-shGRM6-cLRIT3-WPRE) gene therapy. Herein, we demonstrate long-term functional recovery and molecular restoration following subretinal injection of the ON-BC targeting AAV-LRIT3 vector in all eight treated eyes for up to 32 months. Following subretinal administration of the therapeutic vector, expression of the LRIT3 transgene, as well as restoration of mGluR6 signaling cascade member TRPM1, were confirmed in the outer plexiform layer (OPL) of the treated area. However, further investigation of the transgene LRIT3 transcript expression by RNA in situ hybridization (RNA-ISH) revealed off-target expression in non-BCs including the photoreceptors, inner nuclear, and ganglion cell layers, despite the use of a mutant AAV^K9#4 capsid and an improved mGluR6 promoter designed to specifically transduce and promote expression in ON-BCs. While the long-term therapeutic potential of AAV^K9#4-shGRM6-cLRIT3-WPRE is promising, we highlight the necessity for further optimization of AAV-LRIT3 therapy in the canine CSNB model prior to its clinical application.

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LRIT3

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