InsightRP2

InsightRP2 is the first global registry specifically for patients with retinitis pigmentosa caused by changes in the RP2 gene. It collects clinical and genetic information on the causes, medical history, and course of the visual impairment as well as the treatment of the affected individual. We also gather imaging data including images of the back part of the eye (funduscopy; optical coherence tomography, OCT) to analyze how the retina changes in the course of the disease. The InsightRP2 registry helps clinicians and researchers better understand the genetic basis and progression of RP2-associated retinitis pigmentosa. Additionally, they can focus their research and the development of future treatment approaches on enhancing the patients’ quality of life

We aim to find out which types of mutations in the RP2 gene occur more frequently and how individual mutations impact on the age of onset and course of the disease. We also want to learn more about how the disease progresses from the perspective of those affected and whether there are additional associated conditions such as a tendency to rheumatic problems. Additionally, the registry helps to find patients with this particular form of retinitis pigmentosa and to facilitate their access to up-to-date information and potential therapy studies in the future. The registry is set up by the Institute of Human Genetics and uses a secure REDCap-based database hosted at the University Medical Center Göttingen.

InsightRP2 is open to all patients, regardless of sex or age, with a confirmed diagnosis of retinitis pigmentosa caused by a change (pathogenic variant, mutation) in the RP2 gene. Individuals with other types of retinitis pigmentosa are not eligible to enroll in InsightRP2. However, they can, e.g., participate in the registry of the German patient group for degenerative retinal diseases, ProRetina.

Registration process

Participants will register online. To participate in the study, please use one of the following links to the UMG registration site, depending on the patient’s age:

Patient information and consent form – Adults

Patient information and consent form – Adolescents (14-17 years)

Patient information and consent form – Children

For more details on participation and registration, see also our infosheet:

Contact

If you have any questions or are interested in receiving further information about the registry, please send an email to the study manager, Dr. Nina Bögershausen: nina.boegershausen@med.uni-goettingen.de

We collect imaging data such as funduscopic images and optical coherence tomography (OCT) scans. In collaboration with Prof Peter Krawitz and his team at the Institute for Genomic Statistics and Bioinformatics Bonn, we then analyze this data using a specifically programmed artificial intelligence (AI). Our goal is to determine morphological parameters indicative of disease progression.

A key advantage of AI in imaging analysis lies in its ability to detect even subtle changes in the retinal structure at an early stage. For example, AI algorithms can identify decreases in photoreceptor density and changes in the retinal pigment epithelium (RPE) layer with high precision. We aim to exploit these capabilities to objectively describe the progression of RP2-associated RP at an imaging morphological level. We anticipate that this will help to improve clinical diagnosis and follow-up and will inform individual prognosis. Furthermore, we aim to use AI imaging analysis in the process of developing new therapies, as a tool to assess the effectiveness of treatment approaches.

RP2 encodes the RP2 protein, a ubiquitously expressed 350-amino-acid protein. RP2 is expressed throughout the human retina, particularly in the photoreceptor cells’ ciliary apparatus. Within this structure, RP2 plays a crucial role in maintaining ciliary structure and function. RP2 is known to function as a GTPase activating protein (GAP) for the small GTPase ARL3, a ciliary protein vital for transporting proteins to the photoreceptors’ outer segments.

To investigate RP2’s precise function in different retinal cell types, we have been collaborating with the team of Dr Lukas Cyganek (Head of UMG Stem Cell Unit Göttingen, SCU). Using CRISPR/Cas9 technology, we introduced various mutations that have also been identified in patients into induced pluripotent stem cells (iPSCs). These iPSCs are then differentiated into various retinal tissues and organoids, which we analyze in detail by modern high-throughput and OMICS technologies (e.g. single-cell transcriptomics, proteinomics, metabolomics) as well as cell biological and molecular methods. Integrative analysis of OMICS data is performed. We expect these studies to provide new insights into the molecular mechanism of RP2-associated RP.

Insights gained by our molecular studies will guide the development of new therapeutic strategies, focusing on gene replacement and genome editing. Gene therapy holds significant promise for treating degenerative retinal disorders by replacing the defective gene, potentially stabilizing or even improving the affected individual’s vision. A well-known example is Luxturna®, a gene therapy that has been successfully used in patients with RPE65 mutations. Preclinical studies have also demonstrated the feasibility of replacing the RP2 gene through gene therapy, restoring retinal cell function in model systems. These results suggest that gene therapy may also be a viable therapeutic option for RP2-associated RP, in particular as RP2 is a “small” gene and thus easier to be delivered into target cells. We aim to further pursue these approaches to develop a clinically applicable gene therapy for RP2-associated retinitis pigmentosa.