Last update 19 Sep 2024

CRX

Last update 19 Sep 2024

Basic Info

Synonyms

cone-rod homeobox, Cone-rod homeobox protein, CORD2

+ [4]

Introduction

Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with other transcription factors, such as NRL, RORB and RAX, to regulate photoreceptor cell-specific gene transcription. Essential for the maintenance of mammalian photoreceptors.

Drugs associated with CRX

VAR003

Target

CRX

Mechanism

CRX inhibitors

Active Org.

Variant Bio, Inc.Startup

Originator Org.

Variant Bio, Inc.Startup

Active Indication

Cone-Rod Dystrophies [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

VAR001

Target

CRX

Mechanism

CRX inhibitors

Active Org.

Variant Bio, Inc.Startup

Originator Org.

Variant Bio, Inc.Startup

Active Indication

Retinal Diseases

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CRX

100 Translational Medicine associated with CRX

0 Patents (Medical) associated with CRX

588

Literatures (Medical) associated with CRX

05 Jul 2106·Oncotarget

Direct cell fate conversion of human somatic stem cells into cone and rod photoreceptor-like cells by inhibition of microRNA-203

Article

Author: Shin, Ji-Hee ; Choi, Soon Won ; Shin, Tae-Hoon ; Seo, Yoojin ; Kim, Hyung-Sik ; Kim, Jae-Jun ; Kang, Kyung-Sun

Stem cell-based photoreceptor differentiation strategies have been the recent focus of therapies for retinal degenerative diseases. Previous studies utilized embryonic stem (ES) cells and neural retina differentiation cocktails, including DKK1 and Noggin. Here, we show a novel microRNA-mediated strategy of retina differentiation from somatic stem cells, which are potential allogeneic cell sources. Human amniotic epithelial stem cells (AESCs) and umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) treated with a retina differentiation cocktail induced gene expressions of retina development-relevant genes. Furthermore, microRNA-203 (miR-203) is abundantly expressed in human AESCs and human UCB-MSCs. This miR-203 is predicted to target multiple retina development-relevant genes, particularly DKK1, CRX, RORβ, NEUROD1, NRL and THRB. The inhibition of miR-203 induced a retina differentiation of AESCs and UCB-MSCs. Moreover, successive treatments of anti-miR-203 led to the expression of both mature photoreceptor (PR) markers, rhodopsin and opsin. In addition, we determined that CRX, NRL and DKK1 are direct targets of miR-203 using a luciferase assay. Thus, the work presented here suggests that somatic stem cells can potentially differentiate into neural retina cell types when treated with anti-miR-203. They may prove to be a source of both PR subtypes for future allogeneic stem cell-based therapies of non-regenerative retina diseases.

01 Aug 2024·Ophthalmology Retina

Clinical, Genetic and Histopathological Characteristics of CRX-associated Retinal Dystrophies

Article

Author: Boon, Camiel J F ; Hahn, Leo C ; Bergen, Arthur A ; Florijn, Ralph J ; Ten Brink, Jacoline B ; de Carvalho, Emanuel R ; van Schooneveld, Mary J ; Michaelides, Michel ; Georgiou, Michalis ; Webster, Andrew R ; Mahroo, Omar A ; van der Veen, Isa

PURPOSETo describe phenotypic, genotypic, and histopathological features of inherited retinal dystrophies associated with the CRX gene (CRX-RDs).DESIGNRetrospective multicenter cohort study including histopathology.SUBJECTSThirty-nine patients from 31 families with pathogenic variants in the CRX gene.METHODSClinical data of 152 visits were collected from medical records with a median follow-up time of 9.1 years (IQR, 3.3-15.3 years; range, 0.0-48.8 years). Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset CRX-RD was performed.MAIN OUTCOME MEASURESVisual acuity, retinal imaging, electroretinography (ERG), genotype-phenotype correlation, and histopathological examination were evaluated.RESULTSThe age at onset ranged from birth to the 8th decade of life. Median visual acuity was 1.00 logMAR (IQR, 0.69-1.48 logMAR; range, 0.06-3.00 logMAR) at a mean age of 52.0 ± 19.9 years (range, 4.6-81.9 years). Sufficient imaging was available for 36 out of 39 patients (92.3%), and all showed degeneration of at least the macula. Out of these 36 patients, 22 (61.1%) had only macular dystrophy. Another 10 patients (27.8%) had additional degeneration beyond the vascular arcades, and 4 patients (11.1%) panretinal degeneration. Two patients (5.1%) had Leber congenital amaurosis (LCA). In total, 21 different disease-associated heterozygous CRX variants were identified (10 missense, 8 frameshift, 2 deletion, 1 deletion-insertion variants). Missense variants in the CRX homeodomain and two variants deleting all functional domains, thus causing haploinsufficiency, generally tended to cause milder late-onset phenotypes. Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset retinal dystrophy due to a heterozygous deletion of exons 3 and 4 of the CRX gene revealed loss of laminar integrity and widespread photoreceptor degeneration especially in the central retina, with extensive loss of photoreceptor nuclei and outer segments.CONCLUSIONThis study illustrates the large clinical and genetic heterogenic spectrum of CRX-RDs, ranging from LCA to mild late-onset maculopathy resembling occult macular dystrophy. Haploinsufficiency and missense variants tended to be associated with milder phenotypes. Patients showed degeneration predominantly affecting the central retina on imaging. The histopathological findings also mirror these clinical findings and features similar to previously reported animal models of CRX-RDs.

01 Jul 2024·Indian Journal of Ophthalmology

Quality and applicability of cadaveric donor eyes for molecular biology research: An Indian experience

Article

Author: Vishwakarma, Sushma ; Sharma, Sarmeela ; Dave, Tarjani V ; Ali, Mohammed J ; Kaur, Inderjeet ; Kulshrestha, Prerna

Purpose:Human ocular tissue banking plays an important part in the advancement of translational research for identifying the molecular processes involved in disease etiology and pathogenesis. Timely obtaining a good-quality ocular tissue from a cadaveric donor is exceedingly difficult, especially in remote areas, with a variable transportation time (within 12–24 h), raising concerns about RNA quality and its subsequent applications. Therefore, we assessed the utility of retinal tissues from cadaver donor and enucleated eyes based on the RNA quality and gene expression by real-time polymerase chain reaction (PCR).Settings and Design:Prospective study.Methods:Retina tissues were separated from the donor/enucleated eyes received in the eye bank within 24 h of death (n = 15) and within an hour from OR (n = 3), respectively, and stored immediately at -80 degree. RNA was isolated using trizol, and the quantity and quality were assessed using Qubit and agarose gel electrophoresis, respectively. QPCR was performed for measuring the expression of different retinal-specific genes. The cellular viability of the retina was assessed by establishing explant primary cell cultures.Statistical Analysis:The data were calculated as an average of normalised Ct values ± standard error of the mean.Results:RNA obtained from cadaveric tissues despite being partially degraded showed a uniform strong gene expression of several retinal-specific genes such as PAX6, RHO, TUBB3, CRX, and ALDH1L1. The primary cultures established from cadaveric tissues showed viable cells.Conclusion:The cadaver donor tissues collected within 24 hours of death can be effectively utilized for gene expression profiling.

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