Language
Country/Area
No result found
What is Stargardt's disease? How does a genetic defect lead to retinal degeneration?
Stargardt disease is the most common inherited monogenic retinal disease, mainly caused by functional defects in the ABCA4 gene. The disease is inherited in an autosomal recessive manner and causes progressive vision loss in adolescence or adulthood. The main feature of Stargardt's disease is the degeneration of the macular degeneration, the area of the retina responsible for central vision.
Early symptoms of Stargardt's disease include blurred vision, blind spots, and increased sensitivity to light.
Symptoms and signs
Symptoms usually manifest during adolescence or early adulthood and may begin to develop before the age of 20. The main symptom is decreased vision that cannot be corrected with glasses. Sufferers often have trouble reading details or seeing distant objects clearly. Other symptoms include wavy vision, blind spots, blurriness, loss of depth perception, sensitivity to glare, impaired color vision, and poor adaptation to dim conditions (delayed dark adaptation). These symptoms vary greatly between individuals, and the rate of vision loss also varies.
Genetics
The diagnosis of Stargardt's disease has always been based on observation and examination of the eyes, until the recent rise of genetic testing has made the disease more sophisticated. Stargardt disease (STGD1) is caused by biallelic mutations in the ABCA4 gene, while other mimics of Stargardt disease (STGD3 and STGD4) are caused by defects in the PROM1 or ELOVL4 genes. , and it is inherited in an autosomal dominant manner. These gene variants may not only affect vision, but may also be associated with other retinal diseases such as retinitis pigmentosa, cone-rod degeneration, and age-related macular degeneration.
PathophysiologyIn STGD1, a genetic defect causes the ATP-binding groove transporter (ABCA4) in the retina to not function properly. This accelerates the production of toxic vitamin A dimers, the formation of which is considered to be the main cause of the pathological progression. When these dimers damage retinal cells, fluorescent granules called lipofuscin appear in the retinal pigment epithelium as a reflection of the damage. Another type, STGD4, is caused by mutations in the ELOVL4 gene, resulting in a chrysalis-like pattern of pigmentation.
Diagnosis
The diagnosis of Stargardt disease is usually based on clinical history and physical examination, often with slit lamp evaluation. The discovery of characteristic signs can guide further imaging investigations, such as scanning laser fundus imaging, optical coherence tomography, and electrophysiological studies. In some cases, genetic testing is also performed to confirm the diagnosis and avoid incorrect diagnoses.
TreatmentThere is currently no gene therapy for Stargardt disease, but ophthalmologists recommend several measures to potentially slow progression, such as reducing the retina's exposure to harmful ultraviolet light, avoiding excessive intake of vitamin A, and maintaining good overall health. Studies have shown that some patients show improved vision through treatment using bone marrow-derived stem cells. The effects of these treatments may include the transfer of organelles (e.g., mitochondria and lysosomes) and the removal of toxic vitamin A byproducts.
Prognosis
The long-term prognosis of Stargardt disease varies depending on the patient's age at onset and the genetic variant. Although most patients will eventually develop legal blindness, peripheral vision usually remains relatively preserved. Some people with late-onset disease are able to maintain good vision and continue their daily activities for a longer period of time.
EpidemiologyAccording to a 2017 prospective epidemiological study, Stargardt disease occurs in approximately 1 to 1.28 cases per 10,000 people, indicating the relative rarity of the disease.
Research Progress
Currently, many clinical trials are underway, and possible treatments include gene therapy, stem cell therapy, and drug therapy, aiming to test the safety and effectiveness of different therapies. These studies represent a glimmer of hope for treating Stargardt disease, particularly with regard to gene therapy and retinal implants.
There are still many questions to be answered about Stargardt's disease and future treatment possibilities, such as: To what extent can we improve the quality of life of Stargardt's disease patients?
