Retinitis pigmentosa (RP) clinically and genetically heterogeneous group of inherited retinal disorders (IRD) that result in retinal degeneration. This study aimed to identify the genetic findings of patients with autosomal recessive retinitis pigmentosa (arRP). Whole exome sequencing (WES) was performed in two unrelated Pakistani families underlying arRP. Data analysis and mutation screening was performed for all the known RP genes following bi-directional Sanger sequencing to determine whether any of the candidate variants co-segregated with the disease phenotype in the families. WES data analysis revealed a novel homozygous missense variant (c.1274T>C) in the in Tubby like Protein 1 (TULP1 NM_003322.6) gene in family 1 and a novel homozygous frameshift variant (c.351delC) in the retinoid isomerohydrolase 65 (RPE65 NM_000329.3) gene in family 2. The identified variants perfectly co-segregated with the disease phenotype within the families. Our results strongly suggest that mutations in TULP1 and RPE65 are responsible for the retinal phenotype in the affected individuals. These mutations will increase the mutation spectrum of these genes; furthermore, it will enhance our knowledge and understanding of the underlying molecular mechanisms of retinitis pigmentosa.

Both tissue repair and regeneration are a priority in regenerative medicine. Retinitis pigmentosa (RP), a complex retinal disease characterized by the progressive loss of impaired photoreceptors, is currently lacking effective therapies: this represents one of the greatest challenge in the ophthalmological research field. Although this inherited retinal dystrophie is still incurable genetic disease, the oxidative damage is an important pathogenetic element that may represent a viable target of therapy. In this review, we summarize the current neuroscientific evidences about the cell therapies effectiveness, especially based on mesenchymal cells, in RP and focus on their therapeutic actions: limitation of both oxidative stress and apoptotic processes triggered by the disease, promoting cell survival. Cell therapy could therefore represent a feasible therapeutic option in RP.

The aim of this paper is to investigate whether multifractal analysis can be applied to study choroidal blood vessels and help ophthalmologists for the early diagnosis of retinitis pigmentosa (RP). In a case study, we use Spectral Domain Optical Coherence Tomography (SDOCT), which is a non-invasive and highly sensitive imaging technique of the retina and choroid. The image of a choroidal branching pattern can be regarded as a multifractal. Therefore, we calculate generalized Renyi point-centered dimensions, which is considered a measure of inhomogeneity of data, to prove that it increases in the patients with RP with respect to the control group.

Retinitis Pigmentosa, defined more properly as rod-cone dystrophy, is the paradigm of diffuse inherited retinal dystrophies, one of the rare diseases with the highest prevalence in the worldwide population and one of the main causes of low vision in pediatric and elderly age groups. Advancement and understanding in molecular biology and gene editing technologies raised the interest in putting the basis for new therapeutic strategies in rare diseases. As a consequence, new possibilities for clinicians and patients are arising due to the feasibility of treating such a devastating disorder reducing its complications. The scope of this review is to focus on the pathomolecular mechanisms underlying RP better to understand the prospective for its treatment with innovative approaches.

Starvation of photoreceptors induced by reduced dysregulated ocular blood flow (OBF) is proposed as a common pathway for pathogenesis of retinitis pigmentosa (RP). The current study evaluated the safety and efficacy of ophthalmic nerve stimulation (ONS) as an OBF neuromodulator, combined with ascorbic acid (AA) as a potent anti-oxidant in treatment of RP. Additionally, the initial characteristics of rod responders were identified. Forty participants with simple RP, were enrolled in a prospective open-label intervention. The severity of the disease was clinically graded into five stages. Patients with established diagnosis of RP; aged ≥ 4 years, with BCVA ≥ 20/400 were included. All participants were daily treated with bilateral ONS sessions combined with systemic AA for two weeks. The primary efficiency endpoint was 6 months’ changes in scotopic vision as measured by a 10-items, 100 points, Low Luminance Questionnaire- (LLQ-10). The secondary efficiency points included best corrected visual acuity (BCVA) and contrast sensitivity (CS). Rod responders were defined by ≥ 25points increment of LLQ-10 score. The results showed that ONS combined with AA treatment significantly improved night vision, BCVA and CS in patients with RP. At 6-month visit, twenty-four (60%) patients were identified as rod responders and 16 (40%) patients were non-responders. The mean change in LLQ-10 score was (46.35 ±16.81) in rod responders versus (4.9 ± 7.6) in non-responders (P < 0.0001). A clinically significant improvement of BCVA (≥0.2 logMAR) and CS (≥0.3 log unit) were demonstrated in 44.4% and 56.1% of eyes of rod responders respectively. Collectively, this study sheds light on determinants of rod responsiveness which include patients’ age, duration of night blindness and the stage of RP. It also highlights two therapeutic scenarios; an early disease -modifying intervention that restore night vision and reverse the disease process and a late cone rescue intervention that improve/maintain central vision.

To evaluate whether autologous mesenchymal cells, adipose derived stem cells and platelet-rich plasma, grafted into the supracoroideal space by surgical treatment according to Limoli retinal restoration technique (LRRT), can produce growth factors in order to exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and divided based on retinal foveal thickness ≤ 190 or >190 µm into group A and group B, respectively. The specific LRRT triad was grafted in a deep scleral pocket above the choroid of each eye. At 6-month follow-up, group B showed an improvement in residual close-up visus and sensitivity at microperimetry compared to group A. After an in-depth review of molecular biology studies concerning degenerative phenomena underlying the etiopathogenesis of RP, it can be confirmed that further research is needed on tapeto-retinal degenerations both from a clinical and molecular point of view to obtain better functional results. In particular, it is necessary to increase the number of patients, extend observation times, and treat subjects in the presence of still trophic retinal tissue to allow adequate biochemical and functional catering.

Retinitis pigmentosa (RP) is a frequent cause of blindness among the working population in industrial countries, due to the inheritable death of photoreceptors. Though a gene therapy was recently approved for mutations in the RPE65 gene, there is generally no effective treatment presently. Previously, abnormally high-level cGMP and overactivation of its dependent protein kinase (PKG) have been suggested as causative for the fatal effects on photoreceptors, making it meaningful to explore the cGMP-PKG downstream signaling for more pathological insights and novel therapeutic target development purposes. Here we manipulated the cGMP-PKG system in degenerating retinas from the rd1 mouse model pharmacologically via adding a PKG inhibitory cGMP-analogue to organotypic retinal explant cultures. A combination of phosphorylated peptides enrichment and mass spectrometry was then applied to study the cGMP-PKG-dependent phosphoproteomics. We identified a host of novel potential cGMP-PKG downstream substrates and related kinases using this approach, and selected the RAF1 protein, which may act as both a substrate and a kinase, for further validation. We showed that the RAS/RAF1/MAPK/ERK pathway may be involved in retinal degeneration in a yet unclarified mechanism, thus deserving further investigation in the future.

BACKGROUND AND OBJECTIVES. Rod-Cone Dystrophies (RCDs) are genetically determined retinal dystrophies, resulting in nyctalopia, visual field progressive reduction and visual acuity decay in the late stages. Retinitis Pigmentosa (RP) is the most described type. All modes of transmission can be identified in RP, with the autosomal dominant form (ADRP) accounting for about 20% of cases. To date, over 30 genes have been related to ADRP, with RP1 gene estimated to be involved in 5-10% of cases. In a cohort of patients affected by RCD and sharing the same geographic origin from Palermo province in Western Sicily, we identified a prevalent causative variant in the RP1 gene (NM_006269.2; c.2219C>G, p.Ser740*). Objective of our study was to analyse clinical and molecular data of this population and define the entity and the meaning of this finding. MATERIALS AND METHODS. Eighty-four patients with a diagnosis of RCD or RP underwent deep phenotyping, pedigree definition and molecular characterization, mostly by Next Generation Sequencing (NGS). All potentially pathogenic variants have been confirmed through direct sequencing and familial segregation. Statistical evaluation of resulting data has been performed. RESULTS. In 28 probands we identified a pathogenic variant (p.Ser740*) in the RP1 gene that resulted significantly prevalent. Some patients, after careful interviewing, were found to share the same pedigree; we ultimately defined 20 family groups with no traceable consanguinity. CONCLUSIONS. The high prevalence of the p.Ser740* variant in RP patients from Western Sicily unveils the presence of a founder effect, which has implications for the molecular diagnosis of RCD in patients coming from this Italian region. This variant can be primarily searched in RP affected subjects displaying compatible mode of transmission and phenotype, with an advantage in terms of costs and analysis time. Moreover, given its high prevalence, RP1 p.Ser740* variant could represent a potential candidate for the development of therapeutic strategies based on gene editing or translational read-through therapy for suppression of nonsense variants.

Visual impairment and blindness are a growing public health problem, as they reduce the quality of life of millions of people. The management and treatment of these diseases represent a scientific and therapeutic challenge, since the different cellular and molecular actors involved in the pathophysiology are still being identified. The visual system components, particularly the retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune cells activated by insults contribute to biological events that culminate with vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and diseases such as retinitis pigmentosa, age-related macular degeneration, glaucoma and diabetic retinopathy are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cells degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiologic and molecular features, biochemical hallmarks and possible directions for novel treatments, aiming to assist as a guide for innovative research. The expansion of knowledge of the mechanistic bases of the pathobiology of eye diseases, including information on the complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors will allow the identification of new therapeutic strategies.

In golden retriever dogs, a 1 bp deletion in the canine TTC8 gene has been shown to cause progressive retinal atrophy (PRA), the canine equivalent of retinitis pigmentosa. In humans, TTC8 is also implicated in Bardet-Biedl syndrome (BBS). To investigate if the affected dogs only exhibit a non-syndromic PRA or develop a syndromic ciliopathy similar to human BBS, we recruited ten affected dogs to the study. The progression of PRA for two of the dogs was followed for two years, and a rigorous clinical characterization allowed a careful comparison with primary and secondary characteristics of human BBS. In addition to PRA, the dogs showed a spectrum of clinical and morphological signs similar to primary and secondary characteristics of human BBS patients, such as obesity, renal anomalies, sperm defects, and anosmia. We used Oxford Nanopore long-read cDNA sequencing to characterize retinal full-length TTC8 transcripts in affected and non-affected dogs, the results of which suggest that three isoforms are transcribed in the retina, and the 1 bp deletion is a loss-of-function mutation, resulting in a canine form of Bardet-Biedl syndrome with heterogeneous clinical signs.