Model Of Retinitis Pigmentosa Research Articles

Early Alterations of RNA Binding Protein (RBP) Homeostasis and ER Stress-Mediated Autophagy Contributes to Progressive Retinal Degeneration in the rd10 Mouse Model of Retinitis Pigmentosa (RP).

The retinal degeneration 10 (rd10) mouse model is widely used to study retinitis pigmentosa (RP) pathomechanisms. It offers a rather unique opportunity to study trans-neuronal degeneration because the cell populations in question are separated anatomically and the mutated Pde6b gene is selectively expressed in rod photoreceptors. We hypothesized that RNA binding protein (RBP) aggregation and abnormal autophagy might serve as early pathogenic events, damaging non-photoreceptor retinal cell types that are not primarily targeted by the Pde6b gene defect. We used a combination of immunohistochemistry (DAB, immunofluorescence), electron microscopy (EM), subcellular fractionation, and Western blot analysis on the retinal preparations obtained from both rd10 and wild-type mice. We found early, robust increases in levels of the protective endoplasmic reticulum (ER) calcium (Ca2+) buffering chaperone Sigma receptor 1 (SigR1) together with other ER-Ca2+ buffering proteins in both photoreceptors and non-photoreceptor neuronal cells before any noticeable photoreceptor degeneration. In line with this, we found markedly altered expression of the autophagy proteins p62 and LC3, together with abnormal ER widening and large autophagic vacuoles as detected by EM. Interestingly, these changes were accompanied by early, prominent cytoplasmic and nuclear aggregation of the key RBPs including pTDP-43 and FET family RBPs and stress granule formation. We conclude that progressive neurodegeneration in the rd10 mouse retina is associated with early disturbances of proteostasis and autophagy, along with abnormal cytoplasmic RBP aggregation.

Affinity-controlled release of rod-derived cone viability factor enhances cone photoreceptor survival.

Retinitis pigmentosa (RP) is a group of genetic diseases that results in rod photoreceptor cell degeneration, which subsequently leads to cone photoreceptor cell death, impaired vision and eventual blindness. Rod-derived cone viability factor (RdCVF) is a protein which has two isoforms: a short form (RdCVF) and a long form (RdCVFL) which act on cone photoreceptors in the retina. RdCVFL protects photoreceptors by reducing hyperoxia in the retina; however, sustained delivery of RdCVFL remains challenging. We developed an affinity-controlled release strategy for RdCVFL. An injectable physical blend of hyaluronan and methylcellulose (HAMC) was covalently modified with a peptide binding partner of the Src homology 3 (SH3) domain. This domain was expressed as a fusion protein with RdCVFL, thereby enabling its controlled release from HAMC-binding peptide. Sustained release of RdCVFL was demonstrated for the first time as RdCVFL-SH3 from HAMC-binding peptide for 7 d in vitro. To assess bioactivity, chick retinal dissociates were harvested and treated with the affinity-released recombinant protein from the HAMC-binding peptide vehicle. After 6 d in culture, cone cell viability was greater when cultured with released RdCVFL-SH3 relative to controls. We utilized computational fluid dynamics to model release of RdCVFL-SH3 from our delivery vehicle in the vitreous of the human eye. We demonstrate that our delivery vehicle can prolong the bioavailability of RdCVFL-SH3 in the retina, potentially enhancing its therapeutic effects. Our affinity-based system constitutes a versatile delivery platform for ultimate intraocular injection in the treatment of retinal degenerative diseases. STATEMENT OF SIGNIFICANCE: Retinitis pigmentosa (RP) is the leading cause of inherited blindness in the world. Rod-derived cone viability factor (RdCVF), a novel protein paracrine factor, is effective in preclinical models of RP. To extend its therapeutic effects, we developed an affinity-controlled release strategy for the long form of RdCVF, RdCVFL. We expressed RdCVFL as a fusion protein with an Src homology 3 domain (SH3). We then utilized a hydrogel composed of hyaluronan and methylcellulose (HAMC) and modified it with SH3 binding peptides to investigate its release in vitro. Furthermore, we designed a mathematical model of the human eye to investigate delivery of the protein from the delivery vehicle. This work paves the way for future investigation of controlled release RdCVF.

Sigma 1 receptor activation improves retinal structure and function in the RhoP23H/+ mouse model of autosomal dominant retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of devastating inherited retinal diseases that leads to visual impairment and oftentimes complete blindness. Currently no cure exists for RP thus research into prolonging vision is imperative. Sigma 1 receptor (Sig1R) is a promising small molecule target that has neuroprotective benefits in retinas of rapidly-degenerating mouse models. It is not clear whether Sig1R activation can provide similar neuroprotective benefits in more slowly-progressing RP models. Here, we examined Sig1R-mediated effects in the slowly-progressing RhoP23H/+ mouse, a model of autosomal dominant RP. We characterized the retinal degeneration of the RhoP23H/+ mouse over a 10 month period using three in vivo methods: Optomotor Response (OMR), Electroretinogram (ERG), and Spectral Domain-Optical Coherence Tomography (SD-OCT). A slow retinal degeneration was observed in both male and female RhoP23H/+ mice when compared to wild type. The OMR, which reflects visual acuity, showed a gradual decline through 10 months. Interestingly, female mice had more reduction in visual acuity than males. ERG assessment showed a gradual decline in scotopic and photopic responses in RhoP23H/+ mice. To investigate the neuroprotective benefits of Sig1R activation in the RhoP23H/+ mouse model, mutant mice were treated with a high-specificity Sig1R ligand (+)-pentazocine ((+)-PTZ) 3x/week at 0.5 mg/kg and examined using OMR, ERG, SD-OCT. A significant retention of visual function was observed in males and females at 10 months of age, with treated females retaining ∼50% greater visual acuity than non-treated mutant females. ERG revealed significant retention of scotopic and photopic b-wave amplitudes at 6 months in male and female RhoP23H/+ mice treated with (+)-PTZ. Further, in vivo analysis by SD-OCT revealed a significant retention of outer nuclear layer (ONL) thickness in male and female treated RhoP23H/+ mice. Histological studies showed significant retention of IS/OS length (∼50%), ONL thickness, and number of rows of photoreceptor cell nuclei at 6 months in (+)-PTZ-treated mutant mice. Interestingly, electron microscopy revealed preservation of OS discs in (+)-PTZ treated mutant mice compared to non-treated. Taken collectively, the in vivo and in vitro data provide the first evidence that targeting Sig1R can rescue visual function and structure in the RhoP23H/+ mouse. These results are promising and provide a framework for future studies to investigate Sig1R as a potential therapeutic target in retinal degenerative disease.

The photoreceptor protective cGMP-analog Rp-8-Br-PET-cGMPS interacts with cGMP-interactors PKGI, PDE1, PDE6, and PKAI in the degenerating mouse retina.

The inherited eye disease retinitis pigmentosa (RP) causes the loss of photoreceptors by a still unknown cell death mechanism. During this degeneration, cyclic guanosine-3',5'-monophosphate (cGMP) levels become elevated, leading to over-activation of the cGMP-binding protein cGMP-dependent protein kinase (PKG). cGMP analogs selectively modified to have inhibitory actions on PKG have aided in impeding photoreceptor death, and one such cGMP analog is Rp-8-Br-PET-cGMPS. However, cGMP analogs have previously been shown to interact with numerous targets, so to better understand the therapeutic action of Rp-8-Br-PET-cGMPS, it is necessary to elucidate its target-selectivity and hence what potential cellular mechanism(s) it may affect within the photoreceptors. Here, we, therefore, applied affinity chromatography together with mass spectrometry to isolate and identify Rp-8-Br-PET-cGMPS interactors from retinas derived from three different murine RP models (i.e., rd1, rd2, and rd10 mice). Our findings revealed that Rp-8-Br-PET-cGMPS bound seven known cGMP-binding proteins, including PKG1β, PDE1β, PDE1c, PDE6α, and PKA1α. Furthermore, an additional 28 proteins were found to be associated with Rp-8-Br-PET-cGMPS. This latter group included MAPK1/3, which is known to connect with cGMP/PKG in other systems. However, in organotypic retinal cultures, Rp-8-Br-PET-cGMPS had no effect on photoreceptor MAPK1/3 expression or activity. To summarize, Rp-8-Br-PET-cGMPS is more target specific compared to regular cGMP.

Protective effect of ZYMT, a traditional Chinese patent medicine in a mouse model of retinitis pigmentosa

Retinitis pigmentosa (RP) is the most common genetic disorder that causes blindness. At present, there exists no remedy for the disease. The aim of the current research was to investigate the protective effect of Zhangyanming Tablets (ZYMT) in a mouse model of RP, and explore the underlying mechanism. Eighty RP mice were randomly divided into two groups. The mice in ZYMT group were administered with ZYMT suspension(0.0378 g/mL), while the mice in model group were given the same volume of distilled water. At day 7 and day 14 after intervention, electroretinogram (ERG), fundus photography, and histological examination were used to assess the retinal function and structure. TUNEL, immunofluorescence and qPCR were used to evaluate cell apoptosis and expressions of Sirt1, Iba1, Bcl-2, Bax and Caspase-3. A significantly shortened latency of ERG waves was observed in ZYMT-treated mice, in comparison to those in the model group (P < 0.05). Histologically, ultrastructure of the retina was better preserved, and the outer nuclear layer (ONL) exhibited marked increase in thickness and cell count in ZYMP group (P < 0.05). The apoptosis rate was decreased markedly in ZYMT group. Immunofluorescence analysis showed that the expressions of Iba1 and Bcl-2 in the retina were increased, Bax and Caspase-3 were decreased after ZYMT intervention, while the qPCR revealed that the expressions of Iba1 and Sirt1 were significantly increased (P < 0.05). This study indicated that ZYMT has protective effect on retinal function and morphology of inherited RP mice in the early stage, possibly mediated via the regulation of antioxidant and anti-/pro-apoptotic factors expressions.

Eye on genome editing.

CRISPR/Cas9 genome editing techniques have the potential to treat previously untreatable inherited genetic disorders of vision by correcting mutations that cause these afflictions. Using a prime editor, Qin et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20220776) restored visual functions in a mouse model (rd10) of retinitis pigmentosa.

Reduced inspired oxygen decreases retinal superoxide radicals and promotes cone function and survival in a model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is caused by many different mutations that promote the degeneration of rod photoreceptors and have no direct effect on cones. After the majority of rods have died cone photoreceptors begin to slowly degenerate. Oxidative damage contributes to cone cell death and it has been hypothesized that tissue hyperoxia due to reduced oxygen consumption from the loss of rods is what initiates oxidative stress. Herein, we demonstrate in animal models of RP that reduction of retinal hyperoxia by reducing inspired oxygen to continuous breathing of 11% O2 reduced the generation of superoxide radicals in the retina and preserved cone structure and function. These data indicate that retinal hyperoxia is the initiating event that promotes oxidative damage, loss of cone function, and cone degeneration in the RP retina.

In vivo base editing rescues photoreceptors in a mouse model of retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of retinal diseases that cause the progressive death of retinal photoreceptor cells and eventually blindness. Mutations in the β-domain of the phosphodiesterase 6 (Pde6b) gene are the most identified causes of autosomal recessive RP. Clinically, there is no effective treatment so far that can stop the progression of RP and restore the vision. Here, we report a base editing approach in which adeno-associated virus (AAV)-mediated adenine base editor (ABE) delivering to postmitotic photoreceptors was conducted to correct the Pde6b mutation in a retinal degeneration 10 (rd10) mouse model of RP. Subretinal delivery of AAV8-ABE corrected Pde6b mutation with averaging up to 20.79% efficiency at the DNA level and 54.97% efficiency at the cDNA level without bystanders, restored PDE6B expression, preserved photoreceptors, and rescued visual function. RNA-seq revealed the preservation of genes associated with phototransduction and photoreceptor survival. Our data have demonstrated that base editing is a potential gene therapy that could provide durable protection against RP.

Advances in Ophthalmic Epigenetics and Implications for Epigenetic Therapies: A Review

The epigenome represents a vast molecular apparatus that writes, reads, and erases chemical modifications to the DNA and histone code without changing the DNA base-pair sequence itself. Recent advances in molecular sequencing technology have revealed that epigenetic chromatin marks directly mediate critical events in retinal development, aging, and degeneration. Epigenetic signaling regulates retinal progenitor (RPC) cell cycle exit during retinal laminar development, giving rise to retinal ganglion cells (RGCs), amacrine cells, horizontal cells, bipolar cells, photoreceptors, and Müller glia. Age-related epigenetic changes such as DNA methylation in the retina and optic nerve are accelerated in pathogenic conditions such as glaucoma and macular degeneration, but reversing these epigenetic marks may represent a novel therapeutic target. Epigenetic writers also integrate environmental signals such as hypoxia, inflammation, and hyperglycemia in complex retinal conditions such as diabetic retinopathy (DR) and choroidal neovascularization (CNV). Histone deacetylase (HDAC) inhibitors protect against apoptosis and photoreceptor degeneration in animal models of retinitis pigmentosa (RP). The epigenome represents an intriguing therapeutic target for age-, genetic-, and neovascular-related retinal diseases, though more work is needed before advancement to clinical trials.

Phagocytosis in the retina promotes local insulin production in the eye.

The retina is highly metabolically active, relying on glucose uptake and aerobic glycolysis. Situated in close contact to photoreceptors, a key function of cells in the retinal pigment epithelium (RPE) is phagocytosis of damaged photoreceptor outer segments (POS). Here we identify RPE as a local source of insulin in the eye that is stimulated by POS phagocytosis. We show that Ins2 messenger RNA and insulin protein are produced by RPE cells and that this production correlates with RPE phagocytosis of POS. Genetic deletion of phagocytic receptors ('loss of function') reduces Ins2, whereas increasing the levels of the phagocytic receptor MerTK ('gain of function') increases Ins2 production in male mice. Contrary to pancreas-derived systemic insulin, RPE-derived local insulin is stimulated during starvation, which also increases RPE phagocytosis. Global or RPE-specific Ins2 gene deletion decreases retinal glucose uptake in starved male mice, dysregulates retinal physiology, causes defects in phototransduction and exacerbates photoreceptor loss in a mouse model of retinitis pigmentosa. Collectively, these data identify RPE cells as a phagocytosis-induced local source of insulin in the retina, with the potential to influence retinal physiology and disease.

Pharmacochaperones as a novel approach to rescue misfolding rod opsin mutants associated with retinitis pigmentosa.

The correct trafficking of folded, functional rhodopsin (Rho) is critical to sustaining vision. Inherited destabilizing mutations in the rhodopsin (RHO) gene lead to a spectrum of blinding diseases called retinitis pigmentosa (RP) with currently no cure available. Therapeutic approaches to correct these impartments focus on the development of pharmacological chaperones that stabilize rod opsin. The native ligand, 11-cis-retinal, improves protein stability, folding, and trafficking of some mutated Rho variants. However, its chemical instability, toxicity, and poor pharmacokinetics limit its use as a therapeutic. In our laboratory, we focus our attention on finding chaperones with natural-like product scaffolds due to their broad chemical diversity. Furthermore, ∼50% of marketed small molecule drugs are derived from natural products scaffold, and some of them target GPCRs. Thus, we integrated computational, biochemical, biophysical, and in vivo analysis to evaluate non-retinoid ligands with diverse chemical scaffolds as potential chaperones of misfolding Rho variants. Our study led to the discovery of a novel chromenone-containing small molecule with favorable pharmacological properties that through direct binding to the orthosteric pocket enhanced rod opsin stability. This compound improved the membrane trafficking of multiple rod opsin mutants in vitro. Importantly, our studies unraveled the pharmacological potential of this new chromenone rod opsin ligand to slow down the progression of photoreceptor degeneration in the P23H Rho knock-in mice, a model of RP. Together, our studies encourage further search and evaluation of novel non-retinoid compounds that could mitigate the misfolding and mistrafficking of the Rho mutants to prolong the survival of photoreceptors in the retina, and thus delaying vision loss in RP.

Galanin receptor 3 − A new pharmacological target in retina degeneration

The neuropeptide galanin receptor 3 (GALR3) is a class A G protein-coupled receptor (GPCR) broadly expressed in the nervous system, including the retina. GALR3 is involved in the modulation of immune and inflammatory responses. Tight control of these processes is critical for maintaining homeostasis in the retina and is required to sustain vision. Here, we investigated the role of GALR3 in retina pathologies triggered by bright light and P23H mutation in the rhodopsin (RHO) gene, associated with the activation of oxidative stress and inflammatory responses. We used a multiphase approach involving pharmacological inhibition of GALR3 with its antagonist SNAP-37889 and genetic depletion of GALR3 to modulate the GALR3 signaling. Our in vitro experiments in the retinal pigment epithelium-derived cells (ARPE19) susceptible to all-trans-retinal toxicity indicated that GALR3 could be involved in the cellular stress response to this phototoxic product. Indeed, blocking the GALR3 signaling in Abca4-/-/Rdh8-/- and wild-type Balb/cJ mice, sensitive to bright light-induced retina damage, protected retina health in these mice exposed to light. The retina morphology and function were substantially improved, and stress response processes were reduced in these mouse models compared to the controls. Furthermore, in P23H Rho knock-in mice, a model of retinitis pigmentosa (RP), both pharmacological inhibition and genetic ablation of GALR3 prolonged the survival of photoreceptors. These results indicate that GALR3 signaling contributes to acute light-induced and chronic RP-linked retinopathies. Together, this work provides the pharmacological knowledge base to evaluate GALR3 as a potential target for developing novel therapies to combat retinal degeneration.

Application of IPSC and Müller glia derivatives in retinal degenerative diseases.

Retinal degenerative diseases cause blindness characterized by a progressive decline in the number and function of retinal pigment epithelium (RPE), photoreceptor cells, and ganglion cells. Such diseases include retinitis pigmentosa (RP), glaucomatous optic neuropathy, age-related macular degeneration and diabetic optic neuropathy. Recent studies have demonstrated that Müller glial cells (MGCs), an endogenous alternative source of retinal neurons, are important glial cells involved in retinal development, damage, and regeneration, making it an excellent target for retinal nerve regeneration. Although hardly differentiate into neuron cells, transplanted MGCs have been shown to induce partial recovery of visual function in experimental retinal degenerative models. This improvement is possibly attributed to the release of neuroprotective factors that derived from the MGCs. With the development of the therapeutic usage of pluripotent stem cell, application of induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) originated derivation of MGCs have been widely used in retinal degenerative disease model such as glaucoma and retinitis pigmentosa model. This chapter summarized the relevant research and mechanisms and provided a broader application and research prospects for effective treatments in retinal degenerative diseases.

Single-Cell Transcriptomic Profiling of Müller Glia in the rd10 Retina.

Müller glia are the principal macroglia of the retina and support retinal neurons both in health and disease. In retinitis pigmentosa (RP), a highly heterogeneous inherited retinal disorder, the most common form of pathology involves primary rod degeneration, followed by secondary cone death. To investigate Müller glia responses to rod degeneration, we performed droplet-based single-cell RNA sequencing in the rd10 mouse model of RP during primary rod degeneration. We confirmed known MG behavior on gliosis, metabolic, and immune functions. Pde6brd10 Müller glia also exhibited an increased expression of histocompatibility complex members, which might arise from a novel immune function of Müller glia in RP. We also describe a possible decrease in glial lipid biogenesis, which might affect degenerating photoreceptors.

TLR2 Is Highly Overexpressed in Retinal Myeloid Cells in the rd10 Mouse Model of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a genetically heterogeneous disease and the predominant cause of hereditary blindness. Irrespective of the causative mutation, traits common to all forms of RP include photoreceptor dysfunction and death, activation of the retinal glial component, and retinal inflammation. Activation of Toll-like receptors (TLRs) in response to tissue damage is associated with inflammatory processes that contribute to neurodegeneration. We show that retinal expression of the genes Tlr1 to Tlr9 is increased in the rd10 mouse model of RP, with Tlr2 showing the greatest increase (36-fold). Flow cytometry analysis of the retinal myeloid population revealed significant increases in numbers of microglia and infiltrating monocytes and macrophages in rd10 retinas. Furthermore, TLR2 expression, which was restricted to myeloid cells, was increased in rd10 retinal microglia. These observations, together with our previous finding of delayed RP progression following Tlr2 deletion, point to TLR2 as a potential therapeutic target for RP.

An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice.

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy causing progressive vision loss. It is accompanied by chronic and sustained inflammation, including M1 microglia activation. This study evaluated the effect of an essential fatty acid (EFA) supplement containing specialized pro-resolving mediators (SPMs), on retinal degeneration and microglia activation in rd10 mice, a model of RP, as well as on LPS-stimulated BV2 cells. The EFA supplement was orally administered to mice from postnatal day (P)9 to P18. At P18, the electrical activity of the retina was examined by electroretinography (ERG) and innate behavior in response to light were measured. Retinal degeneration was studied via histology including the TUNEL assay and microglia immunolabeling. Microglia polarization (M1/M2) was assessed by flow cytometry, qPCR, ELISA and histology. Redox status was analyzed by measuring antioxidant enzymes and markers of oxidative damage. Interestingly, the EFA supplement ameliorated retinal dysfunction and degeneration by improving ERG recording and sensitivity to light, and reducing photoreceptor cell loss. The EFA supplement reduced inflammation and microglia activation attenuating M1 markers as well as inducing a shift to the M2 phenotype in rd10 mouse retinas and LPS-stimulated BV2 cells. It also reduced oxidative stress markers of lipid peroxidation and carbonylation. These findings could open up new therapeutic opportunities based on resolving inflammation with oral supplementation with SPMs such as the EFA supplement.

Elevated retinal cGMP is not associated with elevated circulating cGMP levels in a canine model of retinitis pigmentosa.

To investigate whether raised levels of retinal cyclic guanosine monophosphate (cGMP) was reflected in plasma levels in PDE6A-/- dogs. Retina was collected from 2-month-old wildtype dogs (PDE6A+/+, N = 6), heterozygous dogs (PDE6A+/-, N = 4) and affected dogs (PDE6A-/-, N = 3) and plasma was collected from 2-month-old wildtype dogs (PDE6A+/+, N = 5), heterozygous dogs (PDE6A+/-, N = 5) and affected dogs (PDE6A-/-, N = 5). Retina and plasma samples were measured by ELISA. cGMP levels in retinal samples of PDE6A-/- dogs at 2 months of age were significantly elevated. There was no significant difference in plasma cGMP levels between wildtype and PDE6A-/- or PDE6A+/- puppies. However, the plasma cGMP levels of the PDE6A-/- puppies were significantly lower than that of PDE6A+/- puppies. cGMP levels in the plasma from PDE6A-/- was not elevated when compared to control dogs. At the 2-month timepoint, cGMP plasma levels would not be a useful biomarker for disease.

P3ht‐Graphene Device for the Restoration of Visual Properties in a Rat Model of Retinitis Pigmentosa

AbstractRetinal degeneration is one of the prevalent causes of blindness worldwide, for which no effective treatment has yet been identified. Inorganic photovoltaic devices have been investigated for visual restoration in advanced stage Retinitis pigmentosa (RP), although lack of implant flexibility and foreign‐object reactions have limited their application. Organic photoactive retinal prostheses may overcome these limitations, being biomimetic and tissue friendly. Inspired by organic photovoltaic strategies involving graphene, a hybrid retinal prosthesis is recently engineered consisting of a dual poly‐3‐hexylthiophene (P3HT) and graphene layer onto a flexible substrate. Here, this hybrid prosthesis is subretinally implanted in vivo in 5‐month‐old Royal College of Surgeons (RCS) rats, a rodent model of RP. Implanted dystrophic rats restored visual performances at both subcortical and cortical levels in response to light stimuli, in the absence of marked inflammatory responses. Moreover, the analysis of the physical‐mechanical properties after prolonged permanence in the eye showed excellent biocompatibility and robustness of the device. Overall, the results demonstrate that graphene‐enhanced organic photovoltaic devices can be suitably employed for the rescue of retinal dystrophies and supports the translation of the organic strategy into medical practice.

Early alterations of RNA binding protein (RBP) homeostasis and ER stress-mediated autophagy trigger progressive retinal degeneration in the rd10 mouse model of retinitis pigmentosa (RP)

Early alterations of RNA binding protein (RBP) homeostasis and ER stress-mediated autophagy trigger progressive retinal degeneration in the rd10 mouse model of retinitis pigmentosa (RP)

Preclinical Models of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is the name for a group of phenotypically-related heritable retinal degenerative disorders. Many genes have been implicated as causing variants of RP, and while the clinical phenotypes are remarkably similar, they may differ in age of onset, progression, and severity. Common inheritance patterns for specific genes connected with the development of the disorder include autosomal dominant, autosomal recessive, and X-linked. Modeling the disease in animals and other preclinical systems offers a cost-conscious, ethical, and time-efficient method for studying the disease subtypes. The history of RP models is briefly examined, and both naturally occurring and transgenic preclinical models of RP in many different organisms are discussed. Syndromic forms of RP and models thereof are reviewed as well.