Frequently Asked Questions

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The RP Gene Research Foundation (RPGRF) is a charitable organization focused on funding research to combat Retinitis Pigmentosa (RP) and other degenerative eye diseases.

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Retinitis pigmentosa (RP) is a group of inherited eye diseases that typically begin in childhood or adolescence. While symptoms can start at different ages for each individual, the first noticeable symptom, often night blindness, commonly appears in the teen years and gradually worsens. Other early signs may include difficulty seeing in dim light and reduced peripheral vision. 

Some individuals may not experience noticeable symptoms until their 40s. The disease progresses slowly, and most people with RP will eventually lose their peripheral vision, leading to tunnel vision. Many individuals are considered legally blind by around age 40, and in advanced stages, central vision may also be affected.   

It is important to note that different genes associated with Retinitis pigmentosa (RP) can lead to variations in disease progression. RP is genetically heterogeneous, meaning mutations in many different genes—over 80 identified—can cause the condition. The specific gene involved can influence the rate of retinal degeneration, age of onset, and severity of vision loss. 

 Yes, children can absolutely get Retinitis Pigmentosa (RP). RP is a genetic disorder that typically begins to manifest in childhood or adolescence. Here's why and how children are affected by RP:

• Genetic Inheritance: RP is primarily caused by mutations in specific genes that control the function of photoreceptor cells (rods and cones) in the retina. These genetic mutations are passed down from parents to children through various inheritance patterns (autosomal dominant, autosomal recessive, X-linked).

• Early Onset of Symptoms: Symptoms often begin to appear during childhood or early adolescence, with the loss of night vision (difficulty seeing in dim light or darkness) being the most common early sign. Parents may notice their child has trouble navigating in the dark or adjusting to dim light.

• Progression of Vision Loss: The disease progresses over time, leading to a gradual loss of peripheral vision (tunnel vision) and eventually central vision as well.

• Variable Severity: The age of onset and rate of progression can vary significantly among individuals, depending on the specific gene mutation and inheritance pattern involved.

• Impact on Daily Life: Children with RP may experience challenges in various activities, such as playing sports, navigating in low-light environments, and reading, depending on the severity of their vision loss.

• Diagnosis and Management: RP is typically diagnosed through a comprehensive eye exam and specialized tests, including genetic testing. Early diagnosis is crucial for implementing strategies to help children manage their vision loss and access appropriate support and resources. 

It is important to remember that:

• While RP can significantly impact a child's vision, most individuals with RP do not completely lose their sight.

• There are resources and support systems available to help children with RP, such as low vision aids, vision rehabilitation programs, and specialized educational plans.

• Genetic counseling can help families understand the inheritance pattern and potential implications of RP for their children.

Retinitis pigmentosa (RP) is diagnosed through a combination of tests performed by an eye doctor, often an ophthalmologist or retina specialist.  Here's how they diagnose RP:

1. Comprehensive Eye Exam:

• Dilated Eye Exam: The eye doctor will dilate your pupils with eye drops to get a clear view of the retina, located at the back of the eye.
• Ophthalmoscopy: Using an ophthalmoscope, the doctor will look for characteristic signs of RP on the retina, such as bone spicule-shaped pigment deposits. 

2. Visual Field Testing:

• Perimetry Tests: These tests measure your peripheral (side) vision to detect blind spots or a narrowed field of vision, common in RP. 

3. Electrophysiological Tests:

• Electroretinogram (ERG): This test measures the electrical activity of the retina's light-sensitive cells (photoreceptors) in response to flashes of light. It helps determine how well the retina is functioning and can detect even early photoreceptor damage. 

4. Imaging Tests:

• Retinal Photography: A camera takes detailed pictures of your retina to document and track the progression of the disease.
• Optical Coherence Tomography (OCT): This non-invasive test uses light waves to create cross-sectional images of the retina, allowing the doctor to analyze its structure and thickness.
• Fundus Autofluorescence (FAF): This test uses blue light to image the retina's natural autofluorescence, highlighting areas of retinal pigment epithelial (RPE) cell dysfunction and degeneration. 

5. Genetic Testing:

• Blood or Saliva Sample: Genetic testing involves analyzing a blood or saliva sample to identify specific gene mutations associated with RP.
• Genetic Counseling: A genetic counselor can explain the testing process, interpret the results, and discuss the implications for the patient and their family. 

Why are these tests important?

• Confirming the Diagnosis: These tests help confirm the presence of RP and rule out other eye conditions.
• Identifying the Specific Type of RP: Genetic testing can help pinpoint the exact gene mutation causing the disease, which can provide insights into how the disease may progress.
• Monitoring Disease Progression: Retinal imaging and visual field tests help track how the disease is affecting the patient's vision over time.
• Assessing Potential for Treatment: Knowing the genetic cause can help determine if the patient might be eligible for future gene therapies or clinical trials. 

In summary, diagnosing Retinitis Pigmentosa involves a comprehensive evaluation of the patient's symptoms, a thorough eye exam, and specialized tests like electroretinography and genetic testing to confirm the diagnosis and determine the specific type of RP. 

Retinitis pigmentosa (RP) is primarily a genetic disorder caused by mutations in genes involved in photoreceptor function. These mutations can be inherited in different patterns: 

1. Autosomal Recessive Inheritance:

• This is the most common pattern, accounting for about 60% of cases.
• It requires inheriting a mutated gene from both parents.
• Parents are typically carriers and do not have the condition themselves.
• Children have a 25% chance of inheriting RP, a 50% chance of being a carrier, and a 25% chance of inheriting neither the gene nor the disorder.
• This form of RP often starts earlier in life with night blindness in childhood. 

2. Autosomal Dominant Inheritance:

• This pattern accounts for about 30% to 40% of cases.
• Only one copy of the mutated gene from one parent is sufficient to cause the condition.
• The affected parent typically has the disorder.
• Each child has a 50% chance of inheriting the mutated gene and thus the disorder.
• This form tends to be less severe and progress more slowly, with symptoms often starting in adulthood. 

3. X-linked Recessive Inheritance:

• This pattern is responsible for about 5% to 15% of cases.
• The mutated gene is located on the X chromosome.
• Males (with one X chromosome) are primarily affected.
• Females (with two X chromosomes) can be carriers, but are less likely to experience severe vision loss.
• Carrier mothers have a 50% chance of having affected sons and a 50% chance of having carrier daughters.
• Affected fathers will pass the mutation to all their daughters (who become carriers) but not to their sons.
• This form often leads to the most severe vision loss. 

4. Sporadic Cases:

• Approximately 50% of RP cases have no documented family history.
• This can occur due to new gene mutations (de-novo mutations) that arise spontaneously in the individual, or in some cases, the inheritance pattern may be unidentifiable. 

Important Notes:

• Genetic Counseling: If RP is suspected in a family, genetic counseling is highly recommended. A genetic counselor can help determine the inheritance pattern, discuss the risk of passing the condition to children, and provide information about genetic testing.
• Genetic Testing: Genetic testing can help identify the specific gene mutation causing RP and provide a more accurate prognosis. 

Understanding the inheritance pattern of RP is crucial for diagnosis, prognosis, and genetic counseling. 

Retinitis pigmentosa (RP) is a highly genetically diverse group of disorders, meaning that mutations in many different genes can lead to the condition. Researchers have identified over 80 genes associated with both syndromic (affecting other organs besides the eye) and non-syndromic forms of RP.  Some of the most common and well-studied genes include: 

• RHO (Rhodopsin): This gene is involved in autosomal dominant RP and accounts for a significant percentage of cases, ranging from 20-30%. It is also responsible for approximately 10% of all RP cases in Europe and the United States. RHO mutations can also lead to autosomal recessive RP and autosomal dominant congenital stationary night blindness (CSNB).

• USH2A: Mutations in this gene are a leading cause of autosomal recessive RP and also the most common cause of Usher syndrome type II (a syndromic form of RP). It accounts for 10-15% of all autosomal recessive RP cases.

• RPGR: This gene is linked to X-linked recessive RP, which is known for its more severe form of vision loss. RPGR mutations account for approximately 70-80% of all X-linked cases.

• PRPH2 (RDS): This gene is associated with autosomal dominant RP. Mutations in PRPH2 can lead to a range of phenotypes, including macular degeneration and other complex maculopathies.

• RP1: Mutations in this gene can cause both autosomal dominant and recessive forms of RP. The inheritance pattern can depend on the type and position of the mutation.

• PRPF31: This gene is a significant cause of autosomal dominant RP and is known for incomplete penetrance, meaning not all individuals with a mutation develop symptoms. It accounts for 1-8% of adRP cases.

• ABCA4: This gene is associated with autosomal recessive RP and is one of the most commonly mutated genes in this category. It is also associated with recessive macular dystrophy and recessive cone-rod dystrophy.

• CRB1: This gene is associated with autosomal recessive RP and is also linked to recessive Leber congenital amaurosis (LCA).

• EYS: This gene is a common cause of autosomal recessive RP, especially in certain populations. It is the largest eye gene and plays a role in the structural integrity of the outer segment of photoreceptors.

• PDE6A and PDE6B: These genes are involved in the phototransduction cascade and can cause autosomal recessive RP.

• RPE65: This gene is linked to autosomal recessive RP and is known for its association with Leber congenital amaurosis (LCA)/early-onset severe retinal dystrophy (EOSRD). Gene therapy is available for patients with mutations in this gene.

• CRX: This gene is a transcription factor involved in photoreceptor development and can cause both autosomal dominant and recessive forms of RP.

• RP2: This gene is another important cause of X-linked recessive RP, accounting for about 10% of cases. Patients with RP2 mutations tend to experience a faster decline in central vision due to early macular atrophy.

• Digenic Inheritance: In rare cases, RP can result from mutations in two different genes, such as PRPH2 and ROM1. This is known as digenic RP.

 Important Notes:

• Genetic Testing: Genetic testing plays a crucial role in diagnosing RP and identifying the specific gene mutation responsible for the condition in an individual.

• Genetic Counseling: If RP is suspected, it is recommended to seek genetic counseling to understand the specific gene involved, its inheritance pattern, and the implications for the individual and their family members. 

The identification of these and many other genes associated with RP is a key step towards developing effective therapies, including gene therapy, to treat this complex group of diseases.  

 While the term "predicable progression" might imply a rigidly uniform course for a given gene mutation, the reality of Retinitis Pigmentosa (RP) is more nuanced due to its high genetic heterogeneity and individual variability. However, scientists have identified strong genotype-phenotype correlations for many RP genes, meaning that specific gene mutations (genotypes) are indeed associated with predictable patterns and rates of progression (phenotypes).

Here's what the research indicates:

• Predictable Patterns, Not Identical Courses: For many identified RP genes, there are general patterns of vision loss that tend to be consistent. For example, some mutations might primarily affect rod photoreceptors first, leading to early night blindness, while others might involve cones earlier, affecting central and color vision more acutely. The sequence of vision loss (e.g., night blindness first, then peripheral, then central) often follows a predictable pattern based on the affected gene.
   
• Severity and Onset Age Correlation:
   
  • X-linked RP (e.g., RPGR and RP2 genes): These forms often lead to earlier onset of symptoms and a more severe and rapid progression of vision loss, particularly in males. Studies have shown faster rates of visual acuity and visual field loss compared to other inheritance patterns.
  • Autosomal Recessive RP (e.g., USH2A, PDE6A, PDE6B genes): These forms generally have an earlier onset than autosomal dominant forms and can have a more severe progression.
  • Autosomal Dominant RP (e.g., RHO, RP1, PRPH2 genes): These typically have a later onset of symptoms and often a milder or slower progression compared to recessive or X-linked forms. However, there can still be variability even within families with the same dominant mutation.

• Gene-Specific Rates of Decline: Research often analyzes the "natural history" of RP linked to specific genes. For instance, studies have compared the mean annual exponential rates of decline in visual acuity, visual field area, and ERG (electroretinogram) amplitude for patients with RPGR mutations versus RHO mutations. This kind of data helps in predicting the general trajectory for individuals with those specific genetic causes.
   
• Influence on Prognosis: Identifying the specific gene mutation through genetic testing is crucial because it can provide significant insights into the likely prognosis, including the typical age of onset, the pattern of vision loss, and the expected rate of progression. This information is invaluable for genetic counseling and for identifying eligibility for gene-specific therapies, such as Luxturna for RPE65 mutations.
   
• Variability Within Genes: It's important to note that even with a strong genotype-phenotype correlation, there can still be some individual variability. Different mutations within the same gene can sometimes lead to different disease severities, and other genetic or environmental factors might play a modifying role. However, the overarching patterns often hold true for common mutations.
   

In summary, while a perfectly "standardized" progression for every single person isn't realistic due to the nuances of human biology, there are very well-established predictable patterns and typical rates of progression associated with many specific RP gene mutations. This makes genetic testing a powerful tool for understanding the likely course of the disease and for guiding clinical management and therapeutic interventions.

 No, not everyone carries a mutated Retinitis Pigmentosa (RP) gene.

Here's why:

• Inherited Condition: RP is a genetic disorder, meaning it's caused by mutations in specific genes. However, these mutations are not present in every person's genetic code.
• Carrier Status: While not everyone has RP, some people can be "carriers" of a mutated RP gene without showing symptoms themselves. This is particularly true for autosomal recessive forms of RP, where an individual needs to inherit two copies of a mutated gene (one from each parent) to develop the condition. Parents who each carry one mutated copy are usually unaffected.
• Prevalence: RP is considered a rare disease, affecting approximately 1 in 3,000 to 1 in 4,000 people worldwide. If everyone carried a mutated RP gene, the prevalence would be much higher.
• Genetic Heterogeneity: There are over 100 different genes that can cause RP. This "genetic heterogeneity" means that different people with RP may have mutations in different genes.

While some studies suggest a relatively high aggregate carrier frequency for recessive RP alleles (meaning the chance of carrying any recessive RP mutation across all possible RP genes), it doesn't mean every single person carries a mutated RP gene. It highlights that many people might unknowingly carry a recessive mutation for a rare genetic condition.

The formation of cataracts in individuals with Retinitis Pigmentosa (RP) is complex and not fully understood, but current research suggests several contributing factors. The most likely explanation points to the following mechanisms: 

1. Inflammation:
   • RP involves a chronic inflammatory response within the eye, driven by the degeneration of photoreceptor cells and retinal pigment epithelial (RPE) cells.
   • This inflammation leads to increased levels of inflammatory cytokines and chemokines in the eye's fluids, such as interleukin (IL)-2, IL-6, IL-10, interferon γ, and monocyte chemoattractant protein-1 (MCP-1).
   • These inflammatory mediators can diffuse into the lens, affecting the lens epithelial cells' normal functions and contributing to cataract formation.
   • The inflammation-induced changes in the intraocular environment are believed to play a critical role in cataract development in RP patients, similar to how inflammation contributes to cataracts in conditions like uveitis.

1. Oxidative Stress:
   • The degeneration of photoreceptors, particularly the rod outer segments, generates reactive oxygen species (ROS) and lipid peroxidation products.
   • These toxic substances can spread into the lens, leading to oxidative stress and damage to lens proteins, particularly crystallins.
   • Oxidative stress disrupts the normal structure and transparency of the lens, causing it to become cloudy and opacify.

1. Lens Epithelial Cell Dysfunction:
   • The lens epithelium, a layer of cells on the front surface of the lens, acts as a barrier that regulates the movement of fluids and nutrients into and out of the lens.
   • In RP patients, abnormalities in the lens epithelium, such as holes and thinning, may allow excessive fluid to enter the lens, disrupting its internal structure and promoting cataract formation.
   • This disruption of lens epithelial cell function can also lead to changes in the lens's metabolic balance and water content, further contributing to cataract development.

1. Accumulation of Degenerative Products:
   • The breakdown products from degenerating photoreceptors and RPE cells may accumulate in the lens, further contributing to lens opacity. 

It's important to note that the exact interplay and relative contributions of these factors are still being investigated, but inflammation and oxidative stress are widely considered the primary drivers of cataract formation in the context of RP.  

Currently, there is no cure for Retinitis Pigmentosa (RP). However, significant research is underway, particularly in the area of gene therapy and cell therapy, that offers hope for future treatments that may slow vision loss or even restore some vision. Here's a summary of the current situation and promising avenues of research:

Current Treatments:

• Gene Therapy:
  • Luxturna® (voretigene neparvovec-rzyl): This is the first FDA-approved gene therapy for inherited retinal diseases and targets mutations in the RPE65 gene. This gene is essential for proper vision, and mutations in both copies of the RPE65 gene can lead to conditions like Leber congenital amaurosis (a severe form of RP). Luxturna provides a functional copy of the RPE65 gene, improving vision in eligible patients.
  • Ongoing Research: Numerous gene therapy trials are exploring treatments for other genes involved in RP, including RPGR, USH2A, and RHO. These therapies aim to replace faulty genes or introduce genetic material that supports retinal cell survival.

• Low Vision Aids and Rehabilitation: These are important for helping individuals adapt to vision loss and maintain independence. This includes using special magnifying glasses, computer programs that translate visual information into spoken words, and occupational therapy programs.

• Vitamins and Supplements: Certain supplements, such as lutein and fish oil (containing DHA), may help slow down RP progression in some cases. However, studies have shown mixed results regarding the overall effectiveness of vitamin A and DHA supplementation for RP.

• Optogenetics: This approach utilizes gene therapy to make retinal cells that are not normally light-sensitive responsive to light. This technology has shown promise in clinical trials, with some patients showing improved visual acuity.

• Retinal Prostheses: Devices like the Argus II are surgically implanted to provide some basic vision restoration in patients with severe vision loss, enabling them to see lines and edges. While new Argus II implants are no longer available, other similar devices are in development.

Promising Future Treatments:

• Cell Therapy:
  • Stem Cell Therapy: Research into using stem cells to replace damaged retinal cells or provide supportive factors to promote retinal cell survival is a major area of focus.
  • CD34+ Stem Cells: A study at UC Davis found that administering CD34+ stem cells into the eyes of RP patients was safe and may offer therapeutic benefits.

• Other Gene Therapies:
  • Mutation-Agnostic Therapies: Some gene therapies are being developed to work regardless of the specific gene mutation causing RP, offering hope for a wider range of patients.
  • CRISPR-Based Gene Editing: This technology holds the potential to edit or correct the mutated genes responsible for RP.

• Photoswitch Therapies: These involve using molecules that bestow light sensitivity to surviving retinal cells. Kiora Pharmaceuticals reported some vision restoration in a clinical trial using this approach. 

In conclusion, while there's no cure for RP yet, the landscape of treatment is rapidly evolving. Gene therapy, particularly the approved Luxturna treatment for RPE65 mutations, represents a significant step forward. Ongoing research into other gene therapies, stem cell-based treatments, and optogenetics offers exciting prospects for slowing or even reversing vision loss caused by RP in the future.  

At present, there is no known way to fully reverse the damage caused by Retinitis Pigmentosa (RP) and completely restore vision. RP is a progressive, inherited eye disease where photoreceptor cells in the retina (rods and cones) break down over time, leading to vision loss. The damage to these cells cannot be completely undone with current treatments. However, the field of RP research is highly active, with promising advancements in therapies and treatments that aim to slow or even partially reverse the vision loss associated with the disease.  

 Important notes:

• Most of these therapies are still in clinical trials.
• The effectiveness of these treatments may vary depending on the individual's specific gene mutation and the stage of the disease.
• Low vision aids and rehabilitation programs are crucial for helping individuals adapt to vision loss and make the most of their remaining vision. 

In summary, while there is no cure for RP, research and clinical trials are exploring various approaches, including gene therapy, cell therapy, and optogenetics, that offer the potential to slow or partially reverse the vision loss associated with this condition. 

Franciscus Cornelius Donders, a Dutch ophthalmologist, is credited with discovering and naming retinitis pigmentosa (RP) in 1857. While his colleague, A.C. van Trigt, provided the first description of RP through an ophthalmoscope in 1853, Donders formally identified and named the condition. 

Here's a more detailed explanation:

• Early Observations: Prior to Donders, ophthalmologists lacked the tools to examine the living retina's interior. The invention of the ophthalmoscope in 1851 allowed for the visualization of the fundus, enabling the correlation of symptoms with observable changes.

• Van Trigt's Contribution: A.C. van Trigt, a student of Donders, used the ophthalmoscope to examine a patient with night blindness and visual field constriction, noting pigment deposits and retinal changes. He published his findings in 1853. 

• Donders' Recognition: In 1857, Donders officially recognized and named the condition "retinitis pigmentosa," acknowledging the pigment deposits and retinal degeneration characteristic of the disease. 

• Significance: RP is now understood as a group of inherited retinal dystrophies causing progressive photoreceptor degeneration. 

 How to Find RP Specialists:

• Foundation Fighting Blindness (FFB): The FFB provides a directory of retina specialists who have experience treating RP and other retinal disorders.

• Academic Medical Centers: University-affiliated medical centers often have ophthalmology departments or retina centers specializing in treating complex eye diseases, including RP.

• Professional Organizations: Organizations like the American Academy of Ophthalmology and the American Society of Retina Specialists may offer directories or resources to help you find specialists in your area.

• Referrals: Your primary eye doctor (optometrist or ophthalmologist) can refer you to a retina specialist in your region.