Current Genetic Eye Disease Research on Fuch’s, Leber’s and Retinitis Pigmentosa

genetic eye diseaseCurrent research on genetic eye diseases focuses mostly on genetic therapies. Scientists have learned how to sequence DNA at a relatively low cost. New tools for modifying genetic materials, such as the CRISPR, have opened the door for new treatments and even cures. Certain eye disorders are caused by mutated genes and genetic predispositions. This article highlights current research into four genetic eye disorders:

  1. Fuchs’ Endothelial Corneal Dystrophy
  2. Leber’s Hereditary Optic Neuropathy
  3. Leber Congenital Amaurosis (congenital retinal blindness)
  4. Retinitis Pigmentosa

Fuchs’ Endothelial Corneal Dystrophy

Fuchs’ Endothelial Corneal Dystrophy causes pain and vision loss in seniors. A person with one parent who has Fuch’s syndrome has a 50% chance of inheriting the disease. The majority of cases show early signs in middle age, and symptoms appear at age 50 and up. Four percent of adults over age 40 develop Fuch’s.

The layer of the cornea called the epithelium helps process water in the cornea. Fuch’s dystrophy patients have fewer endothelial cells than normal. Water builds up, causing the cornea to deteriorate. The Descemet’s membrane thickens, and cysts develop.

  • Doctors may first try to reduce swelling with soft contact lenses or ointments. They may also instruct a patient to use a cool hair dryer directed across the face at arm’s length, several times a day, to dry out the epithelial layer and tear film. In more severe cases, a full or partial corneal transplant may be recommended. However, there is a worldwide shortage of corneas for transplantation. As a result, scientists have made progress in reprogramming adult corneal endothelial cells. They are trying to create progenitor cells. These cells are similar to stem cells but have already started to differentiate. The idea is to graft these cells on the cornea so that the organ can get a fresh start.1
  • Genetic studies found that one gene — TCF4 — was associated Fuchs dystrophy. In 2017, a large team of researchers found three new genetic mutations associated with Fuch’s Dystrophy.2
  • Researchers at Massachusetts Eye and Ear were the first to demonstrate a link between mitochondrial dysfunction and the onset of Fuchs’ dystrophy in 2016.3 They found that oxidative DNA damage over a lifetime leads to malfunction of the mitochondria. Mitochondria provide energy to the cells. The cells of the corneal endothelium begin to die as a result of free radicals. Endothelium cells do not divide in adults and are therefore subject to cumulative DNA damage. They hope to develop novel cytoprotective and anti-aging therapies. See Natural Eye Care’s Page on Antioxidants and Eye Health.
  • More about Fuchs’ Endothelial Corneal Dystrophy

Leber’s Hereditary Optic Neuropathy

Typically, Leber’s Hereditary Optic Neuropathy is passed genetically from mother to son. Males in their teens and twenties begin losing their central vision. This rare condition can affect males and females at any age. Mitochondria, the cell’s source of energy, become mutated in the retinal nerve cells. The genes cannot express themselves properly. Vision loss is rapid and dramatic. Sometimes, vision improves, but rarely.

  • Smoking cigarettes increases the chances of developing the disease in at-risk individuals.4
  • Scientists in Florida are running clinical trials on a virus-based gene transfer treatment for Leber’s Hereditary Optic Neuropathy.5 6 However, results are several years away.
  • Three-person in vitro fertilization could theoretically halt Leber’s Hereditary Optic Neuropathy at conception. Doctors replaced a mother’s mutated mitochondria with healthy donor mitochondria. This technique resulted in the birth of a healthy baby in England in 2016. While the targeted mutation was for fatal Leigh Syndrome, the concept could apply to any mitochondrial disease.
  • See our page on Leber’s Optic Neuropathy

Leber Congenital Amaurosis

Also called congenital retinal blindness, Leber Congenital Amaurosis affects approximately 1 in 40,000 babies. Symptoms include nystagmus (unusual eye movements), unusual pupillary responses, severe vision loss, and even blindness. A parent with the mutation can pass it on to their children.

  • The first successful treatment of a specific mutation that caused Leber Congenital Amaurosis happened in 2008.7 The doctors used an adeno-associated virus to restore vision.
  • Spark Therapeutics’ Voretigene Neparvovec (Luxturna) gene therapy technique was approved as a treatment in December 2017. The target is a mutated RPE65 gene that causes Leber congenital amaurosis.8 This therapy could be useful for other genetic diseases.
  • Nanoparticles have been programmed to seek out retinal cells and deliver genes that could correct Leber Congenital Amaurosis.9 If this works, nanoparticles could deliver corrected genes for many types of conditions.

Retinitis Pigmentosa

In Retinitis Pigmentosa (RP), the photoreceptors and/or the epithelium pigment in the retina degenerate. Serious vision loss can ensue. The disease is a group of inherited vision disorders. RP caused by mutations in more than 60 genes. The rod photoreceptors are damaged, typically effecting one’s peripheral and color vision, as well as ability to quickly adapt from changes in light. This disease affects 100,000 people in the United States, and 1 in 4000 worldwide.10

  • The CRISPR gene editing tool shows potential for reprogramming damaged rod photoreceptors into working cone receptors. Experiments on animals resulted in cellular improvement and restored visual function.11
  • Researchers at MeiraGTx are focusing on RPGR, a mutation that causes Retinitis Pigmentosa. This gene therapy requires injecting healthy copies of RPGR underneath the retina.12
  • NightstaRx was holding Phase I/II clinical trials in 2017 for treating XLRP. Patients with X-linked Retinitis Pigmentosa could benefit. The technique utilizes an adeno-associated viral vector encoding the GTPase Regulator.13
  • Learn more about Retinitis Pigmentosa

Conclusion: Genetic Eye Disease Research

Depending on the disease, a genetic predisposition for an eye disorder does not necessarily result in vision loss. DNA is the basic programming. However, some eye diseases are believed to be triggered by the environment and lifestyle. For example, research shows that people at risk for Leber’s hereditary optic neuropathy should avoid neurotoxins. At Natural Eye Care, we offer many methods for reducing your chances of developing eye diseases. See our pages on the Mediterranean Diet, exercise, supplements, artificial sweeteners, and eye exercises.


  1. Int J Med Sci. 2017 Jun 30;14(8):705-710. doi: 10.7150/ijms.19018. eCollection Characterization and Prospective of Human Corneal Endothelial Progenitors.
  2. Sudha K. Iyengar et. al. Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy. Nature Communications, 2017; 8: 14898 DOI: 10.1038/ncomms14898
  3. New Research Links Mitochondrial Dysfunction to Development of Fuchs’ Endothelial Corneal Dystrophy (FECD), a Common Cause of Corneal Swelling and Blindness, Press Release March 03, 2016, Schepens Eye Research Institute of Massachusetts Eye and Ear
  4. Giordana et al., Cigarette toxicity triggers Leber’s hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways, Cell Death and Disease, December, 2015.
  5. Ophthalmology. Volume 123, Issue 3, March 2016, Pages 558-570. Ophthalmology. Gene Therapy for Leber Hereditary Optic Neuropathy: Initial Results. William J.Feuer MS et al.
  6. Ophthalmology. Available online 21 June 2017. Ophthalmology. Gene Therapy for Leber Hereditary Optic Neuropathy: Low- and Medium-Dose Visual Results. John Guy MD et al.
  7. Maguire AM, Simonelli F, Pierce EA, et al. (May 2008). “Safety and efficacy of gene transfer for Leber’s congenital amaurosis”. Engl. J. Med. 358 (21): 2240–8. PMC 2829748 Freely accessible. PMID 18441370. doi:10.1056/NEJMoa0802315.
  8. Press release, Spark Therapeutics, July 17, 2017.
  9. Molecular Therapy – Nucleic Acids. Targeted Multifunctional Lipid ECO Plasmid DNA Nanoparticles as Efficient Non-viral Gene Therapy for Leber’s Congenital Amaurosis. By Da Sun et. al. Published Online: March 14, 2017. DOI:
  10. UC San Diego Health
  11. Cell Research (2017) 27:830–833. doi:10.1038/cr.2017.57; published online 21 April 2017. Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors. Jie Zhu et al.
  12. MeiraGTx Treats First Patient in XLRP Gene-Therapy Trial By Ben Shaberman. August 30, 2017. Foundation Fighting Blindness.
  13. accessed 9/25/17