Table 2 Summary of patient-derived ROs and RPE cells in IRDs
Type | Gene | Model | Main results | Reference |
|---|---|---|---|---|
RP | PRPF8 c.6974 6994del | RPE cells | Widespread changes in alternative splicing events and dysregulated expression of genes involved in the splicing process and ribosome | [40] |
PRPF31 (1) c.1115_1125del11 (2) c.522_527 + 10del (3) c.709_734dup (4) c.269_273del | ROs and RPE cells | RPE functional and ultrastructural abnormalities, progressive photoreceptor degeneration, impaired pre-mRNA splicing, and disrupted splicing in cellular adhesion and cilia genes | ||
RP2 c.358C > T, p.R120X | ROs | Loss of RP2 protein led to photoreceptor cell death and outer nuclear layer thinning | [167] | |
RPGR c.1415-9A > G | ROs | Mislocalisation of rhodopsin and cone L/M opsin, increased photoreceptor apoptosis, and F-actin dysregulation | [46] | |
USH2A c.8559-2A > G and c.9127_9129delTCC | ROs | Decreased proliferation and laminin expression Abnormal retinal neuroepithelium differentiation and polarization caused defective retinal progenitor cell development and retinal layer formation and disordered organization of neural retina | [53] | |
IMPG2 p.Y254C and p.A805* | ROs | Lack of an outer segment layer and interphotoreceptor matrix disruption due to loss of IMPG2 protein expression or its inability to undergo normal post-translational modifications | [56] | |
CRB1 (1) c.3122T > C, p.M1041T (2) c.2983G > T, p.E995* and c.1892A > G, p.T631C (3) c.2843G > A, p. C948T and c.3122T > C, p.M1041T | ROs | A moderate loss of photoreceptor nuclei in a row, strongly reduced levels of CRB1 variant protein with unaffected CRB1 transcript levels, and a dysregulated molecular gene profiling of Müller glial cells and rods | [168] | |
PDE6B c.694G > A, p.E232K | ROs | Mislocalization of rhodopsin and M-opsin in patient ROs with immature morphology Elevated cGMP levels and significant changes in cGMP hydrolysis-related genes | [169] | |
MERTK (1) c.225delA and c.370C > T, p.Q124* (2) c.225delA | RPE cells | Defective POS phagocytosis | [170] | |
LCA | AIPL1 (1) c.834G > A, p.W278X (2) c.834G > A, p.W278X and c.466-1G > C (3) c.834G > A, p.W278X and c.665 G > A, p.W222X | ROs | Reduced photoreceptor-specific PDE6 and increased cGMP levels | [65] |
CRX (1) c.464_465insGGCA (2) c.262A > C, p.K88Q (3) c.264G > T, p.K88N (4) c.413delT | ROs | Defective photoreceptor maturation and diminished visual opsin expression | ||
CEP290 c.2991 + 1655A > G | ROs and RPE cells | Aberrant splicing and impaired ciliogenesis | ||
LCA5 c.835C > T, p.Q279* | ROs | Lack of lebercilin expression and ciliary localization as well as mislocalization of rhodopsin and cone L/M opsin | [70] | |
IQCB1 (1) c.659delC and c.1362C > T, p.R455X (2) c.421_422delTT and c.1036G > T, p.E346X (3) c.1382C > T, p.R461X and c.1516_1517delCA | ROs and RPE cells | Elongated cilia morphology, impaired development of outer segment structures, and mislocalization of visual proteins | [172] | |
XLRS | RS1 (1) c.625C > T, p.R209C (2) c.488G > A, p.W163X | ROs | Retinal splitting, defective retinoschisin production, abnormal photoreceptor development, and altered paxillin dynamics | [75] |
Batten disease | CLN3 c.175G > A, p.A59T | ROs | Altered pre-mRNA splicing, accumulation of subunit-C of mitochondrial ATPase, mislocalization of peroxisomes, and vacuolization of photoreceptor inner segments | [76] |
Achromatopsia | ATF6 c.1699T > A, p.Y567N and c.970C > T, p.R324C | ROs | Cone defects, increased endoplasmic reticulum stress, Müller cell activation, disrupted mitochondrial structure, and elevated respiratory chain activity gene expression | [77] |
Bestrophinopathy | BEST1 c.229C > T, p.P77S | RPE cells | Impaired bestrophin channel activity | [79] |