Retinal Disorders Research Articles

Chaperonin-Containing TCP1 Subunit 5 Protects Against the Effect of Mer Receptor Tyrosine Kinase Knockdown in Retinal Pigment Epithelial Cells by Interacting With Filamentous Actin and Activating the LIM-Kinase 1/Cofilin Pathway.

Retinitis pigmentosa (RP), characterized by the gradual loss of rod and cone photoreceptors that eventually leads to blindness, is the most common inherited retinal disorder, affecting more than 2.5 million people worldwide. However, the underlying pathogenesis of RP remains unclear and there is no effective cure for RP. Mutations in the Mer receptor tyrosine kinase (MERTK) gene induce the phagocytic dysfunction of retinal pigment epithelium (RPE) cells, leading to RP. Studies have indicated that filamentous actin (F-actin)—which is regulated by chaperonin-containing TCP1 subunit 5 (CCT5)—plays a vital role in phagocytosis in RPE cells. However, whether CCT5/F-actin signaling is involved in MERTK-associated RP remains largely unknown. In the present study, we specifically knocked down MERTK and CCT5 through siRNA transfection and examined the expression of CCT5 and F-actin in human primary RPE (HsRPE) cells. We found that MERTK downregulation inhibited cell proliferation, migration, and phagocytic function; significantly decreased the expression of F-actin; and disrupted the regular arrangement of F-actin. Importantly, our findings firstly indicate that CCT5 interacts with F-actin and is inhibited by MERTK siRNA in HsRPE cells. Upregulating CCT5 using CCT5-specific lentiviral vectors (CCT5-Le) rescued the cell proliferation, migration, and phagocytic function of HsRPE cells under the MERTK knockdown condition by increasing the expression of F-actin and restoring its regular arrangement via the LIMK1/cofilin, but not the SSH1/cofilin, pathway. In conclusion, CCT5 protects against the effect of MERTK knockdown in HsRPE cells and demonstrates the potential for effective treatment of MERTK-associated RP.

Single-cell RNA sequencing of the retina in a model of retinitis pigmentosa reveals early responses to degeneration in rods and cones

BackgroundIn inherited retinal disorders such as retinitis pigmentosa (RP), rod photoreceptor-specific mutations cause primary rod degeneration that is followed by secondary cone death and loss of high-acuity vision. Mechanistic studies of retinal degeneration are challenging because of retinal heterogeneity. Moreover, the detection of early cone responses to rod death is especially difficult due to the paucity of cones in the retina. To resolve heterogeneity in the degenerating retina and investigate events in both types of photoreceptors during primary rod degeneration, we utilized droplet-based single-cell RNA sequencing in an RP mouse model, rd10.ResultsUsing trajectory analysis, we defined two consecutive phases of rod degeneration at P21, characterized by the early transient upregulation of Egr1 and the later induction of Cebpd. EGR1 was the transcription factor most significantly associated with the promoters of differentially regulated genes in Egr1-positive rods in silico. Silencing Egr1 affected the expression levels of two of these genes in vitro. Degenerating rods exhibited changes associated with metabolism, neuroprotection, and modifications to synapses and microtubules. Egr1 was also the most strongly upregulated transcript in cones. Its upregulation in cones accompanied potential early respiratory dysfunction and changes in signaling pathways. The expression pattern of EGR1 in the retina was dynamic during degeneration, with a transient increase of EGR1 immunoreactivity in both rods and cones during the early stages of their degenerative processes.ConclusionOur results identify early and late changes in degenerating rd10 rod photoreceptors and reveal early responses to rod degeneration in cones not expressing the disease-causing mutation, pointing to mechanisms relevant for secondary cone degeneration. In addition, our data implicate EGR1 as a potential key regulator of early degenerative events in rods and cones, providing a potential broad target for modulating photoreceptor degeneration.

Improvement of Retinal Images Affected by Cataracts

Eye fundus images are used in clinical diagnosis for the detection and assessment of retinal disorders. When retinal images are degraded by scattering due to opacities of the eye tissues, the precise detection of abnormalities is complicated depending on the grading of the opacity. This paper presents a concept proof study on the use of the contrast limited adaptive histogram equalization (CLAHE) technique for better visualization of eye fundus images for different levels of blurring due to different stages of cataracts. Processing is performed in three different color spaces: RGB, CIELAB and HSV, with the aim of finding which one better enhances the missed diagnostic features due to blur. The experimental results show that some fundus features not observable by naked eye can be detected in some of the space color processed with the proposed method. In this work, we also develop and provide an online image process, which allows clinicians to tune the default parameters of the algorithm for a better visualization of the characteristics of fundus images. It also allows the choice of a region of interest (ROI) within the images that provide better visualization of some features than those enhanced by the processing of the full picture.

AAV-CRISPR/Cas9 Gene Editing Preserves Long-Term Vision in the P23H Rat Model of Autosomal Dominant Retinitis Pigmentosa.

Retinitis pigmentosa (RP) consists of a group of inherited, retinal degenerative disorders and is characterized by progressive loss of rod photoreceptors and eventual degeneration of cones in advanced stages, resulting in vision loss or blindness. Gene therapy has been effective in treating autosomal recessive RP (arRP). However, limited options are available for patients with autosomal dominant RP (adRP). In vivo gene editing may be a therapeutic option to treat adRP. We previously rescued vision in neonatal adRP rats by the selective ablation of the Rhodopsin S334ter transgene following electroporation of a CRISPR/Cas9 vector. However, the translational feasibility and long-term safety and efficacy of ablation therapy is unclear. To this end, we show that AAV delivery of a CRISPR/Cas9 construct disrupted the Rhodopsin P23H transgene in postnatal rats, which rescued long-term vision and retinal morphology.

The Role of Heat Shock Proteins in Systemic Vascular Catastrophes and in Acute Vascular Diseases of an Eye

The disruption of blood flow through the retinal vessels is undoubtedly a stressful situation for the body. In response to any stress, the body produces heat shock proteins or so-called stress proteins. Moreover, a number of modern studies indicate that HSP may act as autoantigens, which are components of the immune system involved in the pathogenesis of vascular pathologies. By now, a number of certain heat shock proteins (HSP 60, 70) have already been proven to play a significant role in the pathogenesis of atherosclerosis as well as various circulatory disorders in the cerebral vessels. In addition, the possibility of using the data on the content and concentration of certain HSPs and antibodies to them in the blood plasma of patients as diagnostic and prognostic markers of systemic vascular diseases is considered. On the visual organ side, HSPs have been found to have damaging effects on retinal ganglion cells and, together with antibodies produced in response to their presence, are involved in the pathogenesis of glaucoma. However, there is currently no data on the role of HSP in the pathogenesis of retinal blood flow disorders and the possibility of using these molecules as diagnostic or prognostic markers of such conditions.

Frequency of cystoid macular edema and vitreomacular interface disorders in genetically solved syndromic and non-syndromic retinitis pigmentosa.

Retinitis pigmentosa (RP) corresponds to a group of inherited retinal disorders where progressive rod-cone degeneration is observed. Cystoid macular edema (CME) and vitreomacular interface disorders (VMID) are known to complicate the RP phenotype, challenging an age-old concept of retained central visual acuity. The reported prevalence of these changes varies greatly among different studies. We aim to describe the frequency of CME and VMID and identify predictors of these changes in a cohort of Caucasian patients with genetically solved syndromic (sRP) and non-syndromic RP (nsRP). Cross-sectional study of patients with genetically solved sRP or nsRP. Genetic testing was clinically oriented in all probands and coordinated by a medical geneticist. The presence/absence of CME and VMIDs such as epiretinal membrane (ERM), vitreomacular traction (VMT), lamellar hole (LH), macular hole (MH), and macular pseudohole (MPH), and the integrity of the neurosensory retina and retinal pigment epithelium were evaluated in individual macular SD-OCT b-scans. Mixed-effects regression analysis models were used to identify significant predictors of BCVA, CME, and VMID. Significance was considered at α < 0.05. We included 250 eyes from 125 patients. Mean age was 44.9 ± 15.7years and 55.2% were male. Eighty-eight patients had nsRP and 37 had sRP. Median BCVA was 0.5 (0.2-1.3) logMAR. CME was found in 17.1% of eyes, while ERM was found in 54.3% of eyes. The frequency of CME (p = 0.45) and ERM (p = 0.07) did not differ between sRP and nsRP patients, nor across different inheritance patterns. Mixed-effects univariate linear regression identified age (p = 0.04), cataract surgery (p < 0.01), and loss of integrity of outer retinal layers (p < 0.01) as significant predictors of lower visual acuity, while increased foveal thickness (p < 0.01) and the presence of CME (p = 0.04) were predictors of higher visual acuity. On mixed-effects multivariable analysis, only increased foveal thickness was significantly associated with better visual acuity (p < 0.01). We found that the burden of ERM and CME in RP patients is high, highlighting the importance of screening for these potentially treatable conditions to improve the quality of life of RP patients.

The effect of hyperbaric oxygen therapy on retina, choroidal thickness, and choroidal vascularity index

PurposeTo determine the acute and cumulative effect of hyperbaric oxygen therapy (HBOT) on retina and choroid tissue in healthy eyes. Material and methodsThirty-five subjects who were planned to undergo HBOT for non-ophthalmologic indications comprised the population of this prospective study. Central macular thickness (CMT), retinal nerve fiber layer (RNFL), and choroidal thickness (CT) (3 points: subfoveal area, 500 µm nasal and fovea temporal) were measured using spectral-domain optical coherence tomography (SD-OCT) before HBOT and half an hour after the 1st and 20th sessions of HBOT. The subfoveal choroidal area was segmented using ImageJ software with the binarization technique on enhanced depth imaging (EDI) OCT images. Choroidal area (CA), luminal area (LA), and stromal area (SA) were calculated. Choroidal vascularity index (CVI) was determined as the ratio between LA and CA. ResultsThe right eyes of 35 patients aged between 22 and 59 years were enrolled in the study. The mean CMT values of the patients were 259.36 ± 22.31 µm, 256.94 ± 22.72 µm, and 254.58 ± 23.02 µm before HBOT, after the 1st session, and after the 20th session, respectively. The change in CMT values before and after HBOT was statistically significant (p=0.001). When the patients' RNFL, CT, CA, SA, LA, and CVI changes before and after the HBOT were examined, no statistically significant difference was found (p>0.05). ConclusionsOur study jointly evaluates the effect of HBOT on the vascular and stromal components of the choroid and macula in healthy eyes. Due to its thinning effect on the macula, it can be preferred as an adjunctive and facilitating treatment option in addition to current treatments in patients with macular edema due to retinal vascular disorders.

Detection of retinal disorders from OCT images using generative adversarial networks

Detection of retinal disorders from OCT images using generative adversarial networks

Applying Protein-Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis.

Retinitis Pigmentosa (RP) is a hereditary retinal disorder that causes the atrophy of photoreceptor rod cells. Since individual defective genes converge on the same disease, we hypothesized that all causal genes of RP belong in a complex network. To explore this hypothesis, we conducted a gene connection analysis using 161 genes attributed to RP, compiled from the Retinal Information Network, RetNet. We then examined the protein interaction network (PIN) of these genes. In line with our hypothesis, using STRING, we directly connected 149 genes out of the recognized 159 genes. To uncover the association between the PIN and the ten unrecalled genes, we developed an algorithm to pinpoint the best candidate genes to connect the uncalled genes to the PIN and identified ten such genes. We propose that mutations within these ten genes may also cause RP; this notion is supported by analyzing and categorizing the known causal genes based on cellular locations and related functions. The successful establishment of the PIN among all documented genes and the discovery of novel genes for RP strongly suggest an interconnectedness that causes the disease on the molecular level. In addition, our computational gene search protocol can help identify the genes and loci responsible for genetic diseases, not limited to RP.

Dexamethasone Intravitreal Implant for the Treatment of Macular Edema and Uveitis: A Comprehensive Narrative Review.

PurposeThe purpose of this review article is to provide a comprehensive review of the current applications of intravitreal DEX implant (Ozurdex®, Allergan Inc, Irvine, CA) for a variety of ophthalmic conditions – ranging from FDA approved indications to off-label uses. We have attempted to provide relevant evidence from the literature to help a reader develop an understanding of the biological and pharmacokinetic properties of DEX implant, its uses, and potential side effects.MethodsPubMed searches were performed using the terms “Ozurdex”, or “intravitreal DEX implant”, AND “retinal vein occlusion”, or “diabetic macular edema”, or “uveitis”. The search was performed in July of 2021, with an additional search in October 2021. All original English language articles were considered for this review.ResultsDEX implant has evidence of efficacy in a variety of clinical situations including macular edema associated with retinal vein occlusion, diabetes, uveitis, and others. Safety concerns include cataract formation and progression, intraocular pressure elevation, complications related to intravitreal injection, and opportunistic infections secondary to steroid-induced immune suppression.ConclusionDEX implant is a useful tool in the management of several retinal disorders. Further studies are needed for head-to-head comparison with other treatment modalities and to determine its precise place in clinical practice.

Health Equity and Disparities in ROP Care: A Need for Systematic Evaluation.

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disorder that can have devastating visual sequelae if not managed appropriately. From an ophthalmology standpoint, ROP care is complex, since it spans multiple care settings and providers, including those in the neonatal intensive care unit (NICU), step down nurseries, and the outpatient clinic setting. This requires coordination and communication between providers, ancillary staff, and most importantly, effective communication with the patient's family members and caregivers. Often, factors related to the social determinants of health play a significant role in effective communication and care coordination with the family, and it is important for ophthalmologists to recognize these risk factors. The aim of this article is to (1) review the literature related to disparities in preterm birth outcomes and infants at risk for ROP; (2) identify barriers to ROP care and appropriate follow up, and (3) describe patient-oriented solutions and future directions for improving ROP care through a health equity lens.

A Systematic Review of Artificial Intelligence Applications Used for Inherited Retinal Disease Management.

Nowadays, Artificial Intelligence (AI) and its subfields, Machine Learning (ML) and Deep Learning (DL), are used for a variety of medical applications. It can help clinicians track the patient’s illness cycle, assist with diagnosis, and offer appropriate therapy alternatives. Each approach employed may address one or more AI problems, such as segmentation, prediction, recognition, classification, and regression. However, the amount of AI-featured research on Inherited Retinal Diseases (IRDs) is currently limited. Thus, this study aims to examine artificial intelligence approaches used in managing Inherited Retinal Disorders, from diagnosis to treatment. A total of 20,906 articles were identified using the Natural Language Processing (NLP) method from the IEEE Xplore, Springer, Elsevier, MDPI, and PubMed databases, and papers submitted from 2010 to 30 October 2021 are included in this systematic review. The resultant study demonstrates the AI approaches utilized on images from different IRD patient categories and the most utilized AI architectures and models with their imaging modalities, identifying the main benefits and challenges of using such methods.

Retinal Circular RNA hsa_circ_0087207 Expression Promotes Apoptotic Cell Death in Induced Pluripotent Stem Cell-Derived Leber's Hereditary Optic Neuropathy-like Models.

Backgrounds: Leber’s hereditary optic neuropathy (LHON) is known as an inherited retinal disorder characterized by the bilateral central vision loss and degeneration of retinal ganglion cells (RGCs). Unaffected LHON carriers are generally asymptomatic, suggesting that certain factors may contribute to the disease manifestations between carriers and patients who carry the same mutated genotypes. Methods: We first aimed to establish the iPSC-differentiated RGCs from the normal healthy subject, the carrier, and the LHON patient and then compared the differential expression profile of circular RNAs (CircRNAs) among RGCs from these donors in vitro. We further overexpressed or knocked down the most upregulated circRNA to examine whether this circRNA contributes to the distinct phenotypic manifestations between the carrier- and patient-derived RGCs. Results: iPSCs were generated from the peripheral blood cells from the healthy subject, the carrier, and the LHON patient and successfully differentiated into RGCs. These RGCs carried equivalent intracellular reactive oxygen species, but only LHON-patient iPSC-derived RGCs exhibited remarkable apoptosis. Next-generation sequencing and quantitative real-time PCR revealed the circRNA hsa_circ_0087207 as the most upregulated circRNA in LHON-patient iPSC-derived RGCs. Overexpression of hsa_circ_0087207 increased the apoptosis in carrier iPSC-derived RGCs, while knockdown of hsa_circ_0087207 attenuated the apoptosis in LHON-patient iPSC-derived RGCs. Predicted by bioinformatics approaches, hsa_circ_0087207 acts as the sponge of miR-665 to induce the expression of a variety of apoptosis-related genes in LHON patient iPSC-derived RGCs. Conclusions: Our data indicated that hsa_circ_0087207 upregulation distinguishes the disease phenotype manifestations between iPSC-derived RGCs generated from the LHON patient and carrier. Targeting the hsa_circ_0087207/miR-665 axis might hold therapeutic promises for the treatment of LHON.

Etiopathogenesis of non-exudative age-related macular degeneration (literature review)

The article presents an overview of modern publications on epidemiology, risk factors, and the main links of the etiology and pathogenesis of age-related macular degeneration (AMD). The nonexudative or “dry” form of age-related macular degeneration is a multifactorial progressive pathological process caused by hereditary predisposition, general and local disorders of lipid metabolism, negative changes in the blood supply to the eye, age-related destruction of the Bruch’s membrane and retinal pigment epithelium, the appearance of signs of local and systemic inflammation, the development of oxidative stress with the impact of toxic lipoperoxidation products on the structures of the posterior segment of the eye. Recent studies have discovered new ways of retinal pigment epithelial cell death in response to oxidative stress in AMD, in particular necroptosis, which, in addition to classical apoptosis, is considered the main mechanism of this process. It is noted that the development of AMD may be associated with an age-related decrease in the level of estrogen in women. The analysis of the data on the etiopathogenesis of age-related macular degeneration presented in the modern literature indicates the need for further research and generalization of local and general pathological processes developing in the dynamics of retinal visual function disorders by specialists of various scientific disciplines.

Retinoic acid inhibitors mitigate vision loss in a mouse model of retinal degeneration.

Rod and cone photoreceptors degenerate in retinitis pigmentosa (RP). While downstream neurons survive, they undergo physiological changes, including accelerated spontaneous firing in retinal ganglion cells (RGCs). Retinoic acid (RA) is the molecular trigger of RGC hyperactivity, but whether this interferes with visual perception is unknown. Here, we show that inhibiting RA synthesis with disulfiram, a deterrent of human alcohol abuse, improves behavioral image detection in vision-impaired mice. In vivo Ca2+ imaging shows that disulfiram sharpens orientation tuning of visual cortical neurons and strengthens fidelity of responses to natural scenes. An RA receptor inhibitor also reduces RGC hyperactivity, sharpens cortical representations, and improves image detection. These findings suggest that photoreceptor degeneration is not the only cause of vision loss in RP. RA-induced corruption of retinal information processing also degrades vision, pointing to RA synthesis and signaling inhibitors as potential therapeutic tools for improving sight in RP and other retinal degenerative disorders.

Corneal laser procedure for vision improvement in patients with neovascular age-related macular degeneration and other retinal disorders involving central vision loss: a retrospective cohort study

Background: The purposes of this pilot retrospective observational cohort study are to determine: 1) the safety and efficacy of corneal photovitrification (CPV), a corneal laser procedure, for vision improvement in patients with neovascular age-related macular degeneration (nAMD) and other retinal disorders involving central vision loss, and 2) the correlation between post-treatment (post-treatment (Tx)) best-corrected distance visual acuity (BCDVA) and pre-Tx potential visual acuity (PVA). Methods: BCDVA measurements using ETDRS charts and PVA measurements using Gonzalez-Markowitz PVA charts were analyzed for 72 eyes that received a single CPV treatment. Results: Safety - No clinically significant complications or serious adverse events occurred. Efficacy – Mean BCDVA improved significantly from 20/303 (1.18 log of the minimum angle of resolution (logMAR), 26 letters) at pre-Tx to 20/208 (1.02 logMAR, 34 letters) at 1m post-Tx (p = 0.000001) for a cohort of 57 eyes, improving to 20/198 (1.00 logMAR, 35 letters; 11.6 mean letters gained) at 12m (p = 0.0009) for a cohort of 29 eyes. Mean pre-Tx PVA gains correlated well with mean BCDVA improvements at 1m, 3m, 6m and 12m post-Tx. Conclusions: Subject to a small sample size, the CPV corneal laser procedure is safe and efficacious for vision improvement in patients with nAMD and other retinal disorders involving central vision loss. The pre-Tx PVA correlates well with post-Tx BCDVA; the PVA test may be useful for screening of candidate eyes for CPV treatment and for managing expectations.

Retinopathy of prematurity: A revisit to the incidence, risk factors, and its response to laser therapy

: The debilitating vasoproliferative retinal disorder retinopathy of prematurity (ROP), a prequel to neonatal blindness is known to be increasing in recent years with improved advances in neonatal care and survival. Aim of this study was to study the incidence of ROP, risk factors, and response to the gold standard treatment of laser has been explored in this study.: In this prospective observational study of all neonates referred to the retina clinic of a tertiary care centre, from both in-house referrals and peripheral centres. Demographic data, both maternal and neonatal data were recorded. Neonates complying to inclusion and exclusion criteria were examined under 28 diopter lens and all ROP were documented using RetCam. Laser photocoagulation was performed and later followed up according to ETROP schedule.: 699 neonates were screened in the study and ROP was detected in 13.73% (182/1398) of this population, with mean gestational age 31.82±2.44 weeks and mean birth weight 1425.36±287.73 grams. Neonatal risk factors of gestational age &amp;#60;34 weeks, low birth weight, ventilatory support, RDS, oxygen supplementation, sepsis, birth asphyxia, blood transfusion, and phototherapy were found to have significant association for incidence of ROP and those requiring treatment. When 67.58% regressed spontaneously, all 59 eyes requiring treatment underwent laser therapy. 46 out of these 59 eyes (77.97%) showed regression and remaining seven eyes required further intervention.: Better premature neonates survival rates has shown an increased incidence of ROP over the past decades. Red flag signs like low gestational age, low birth weight, RDS, oxygen supplementation, sepsis, blood transfusion, AGA and twin pregnancy are confirmed to have significant association with the development of ROP. Laser therapy still remains effective in controlling progression of the disease.

Identification of a novel compound heterozygous CYP4V2 variant in a patient with autosomal recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) belongs to a family of retinal disorders that is characterized by the progressive degeneration of rod and cone photoreceptors. The aim of the present study was to screen for possible disease-causing genetic variants in a non-consanguineous Chinese family with non-syndromic autosomal recessive RP. Whole-exome sequencing (WES) was performed in samples from the affected individual (the proband) and those from the two children of the proband. A novel compound heterozygous variant of c.C958T (p.R320X) and c.G1355A (p.R452H) in the Cytochrome P450 family 4 subfamily V member 2 (CYP4V2) gene was identified through WES. Subsequently, this variant was validated by direct Sanger sequencing. This compound heterozygous variant was found to be absent from other unaffected family members and 400 ethnically-matched healthy control individuals. In addition, this compound variant was co-segregated with the RP phenotype in an autosomal recessive manner. In silico analysis revealed that both c.C958T (p.R320X) and c.G1355A (p.R452H) could compromise the protein function of CYP4V2. These results strongly suggest this compound variant to be a disease-causing variant, which expands upon the spectrum of currently known CYP4V2 genetic variants associated with retinal diseases.

Retinopathy of prematurity: contribution of inflammatory and genetic factors.

Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder that represents an important cause of childhood visual impairment and blindness. Although oxidative stress has long been implicated in ROP etiology, other prenatal and perinatal factors are also involved. This review focuses on current research involving inflammation and genetic factors in the pathogenesis of ROP. Increasing evidence suggests that perinatal inflammation or infection contributes to ROP pathogenesis. Cytokines and chemokines with a fundamental role in inflammatory responses and that significantly contributing to angiogenesis are analyzed. Microglia cells, the retinal-resident macrophages, are crucial for retinal homeostasis, however, under sustained pathological stimuli release exaggerated amounts of inflammatory mediators and can promote pathological neovascularization. Current modulation of angiogenic cytokines, such as treatment with antibodies to vascular endothelial growth factor (anti-VEGF), has shown efficacy in the treatment of ocular neovascularization; however, some patients are refractory to anti-VEGF agents, suggesting that other angiogenic or anti-angiogenic cytokines need to be identified. Much evidence suggests that genetic factors contribute to the phenotypic variability of ROP. Several studies have implicated the involvement of candidate genes from different signaling pathways in the development of ROP. However, a genetic component with a major impact on ROP has not yet been discovered. Most studies have limitations and did not replicate results. Future research involving bioinformatics, genomics, and proteomics may contribute to finding more genes associated with ROP and may allow discovering better solutions in the management and treatment of ROP.

Topical Ocular Administration of Progesterone Decreases Photoreceptor Cell Death in Retinal Degeneration Slow (rds) Mice.

Retinitis pigmentosa (RP) is an inherited eye disorder which triggers a cascade of retinal disorders leading to photoreceptor cell death and for which there is currently no effective treatment. The purpose of this research was to study whether ocular administration of a solution of progesterone (PG) in β-cyclodextrins (CD) could delay photoreceptor cell death and counteract the gliosis process in an animal model of RP (rds mice). The possible effect of PG reaching the contralateral eye through the circulatory system was also evaluated. Finally, this research discusses and evaluates the diffusion of the drug from possible topical formulations for ocular administration of PG. A group of rds mice received one drop of a solution of PG in CD every 12 h for 10 days to the left eye, while the right eye was left untreated. Another group of rds mice (control) received the drug vehicle (PBS) on the left eye and, again, the right eye was left untreated. Once the treatment was finished on postnatal day 21, the animals were euthanized and histological immunofluorescence studies (TUNEL, GFAP, and DAPI staining) were carried out. Our results showed that the administration of a solution of PG in CD (CD-PG) as drops significantly decreased cell death and inflammation in the retina of the PG-treated eyes of rds mice. No effect was seen in the contralateral eye from PG that may have entered systemic circulation. In conclusion, CD-PG applied topically as drops to the eye decreases photoreceptor cell death in the early stages of RP, delaying vision loss and decreasing gliosis.