The eyes are one of the essential organs of the human body. They help in visualization and play a vital role in facial esthetics and communications. Some ocular disorders are almost impossible to treat. Retinal degenerative disorders are a group of diseases that may lead to total blindness or incurable conditions.
Retinal degenerative disorders are hereditary progressive disorders affecting one in every 4000 people worldwide. So far, almost 120 genes responsible for these disorders have been identified. Furthermore, different pathogenesis makes the treatment of these conditions a complex procedure. Recent advancements in gene therapy can potentially treat various forms of retinal degeneration. Development in gene therapy is helpful in the early identification of the genetic factor, and replacing defective genes helps eliminate the disease.
What Is Retinal Degenerative Disorder?
Retinal degenerations are X-linked genetic disorders. Different photoreceptor cells are affected as various genes are responsible for these conditions. Based on that, these diseases can be categorized into the following:
1) Rod and Rod-Cone Dystrophies: In this condition, rod photoreceptors or rod cells are affected first, followed by cone cells. These disorders can be categorized into two types:
Retinitis Pigmentosa: This is the most common type of disorder, which is progressive and nonsyndromic. Almost 60 genes have been identified so far as responsible for this condition. 15 % to 20 % of cases are autosomal dominant, 5 % to 15 % are autosomal recessive, 5 % to 15 % are X-linked, and 40 % to 50 % are of unknown inheritance. ROM1 and PRPH2 are two genes responsible for inheritance. Mutations in the gene RHO is one of the main causative factors causing impaired rhodopsin production.
The symptoms of the disease are first observed at a young age, starting with night vision problems and progressing to peripheral vision loss. The clinical features are:
The waxy pallor of the optic disc.
Narrowing of the blood vessels.
Bony spicule-type pigmentation of the retina.
Congenital Stationary Night Blindness: This is a non-progressive type of night blindness. Eleven genes like CACNA1F, CACNA2D4, TRPM1 are responsible for this condition. The clinical findings of this condition are:
A golden sheen is present over the retina.
The macula is dark.
Color vision and visual acuity are normal.
Yellow-white dots are present over the fundus.
Presence of an abnormal layer of tissue in between retinal pigmented epithelium and photoreceptors.
2) Progressive Cone and Cone-Rod Dystrophies:
In this condition, the cone photoreceptors are involved or affected, followed by rod cells. ABCA4 is the most common gene associated with this disorder. This condition is again subdivided into several types.
Cone Monochromatism: This is an X-linked recessive disorder. Two out of the three cone systems in this condition are either affected or absent. The most common variety is blue monochromatism, where red and green systems are completely absent.
Cone Rod Dystrophy: The clinical presentation is similar to that of retinitis pigmentosa. Common complications include early vision loss, color vision abnormalities, and peripheral vision loss. Fundus examination reveals the following findings:
Achromatopsia: This is an autosomal recessive condition that affects patients from birth. Complete achromatopsia causes a complete loss of visual acuity and red monochromatism. Partial loss of visual acuity can be seen in incomplete achromatopsia. Clinical features of this condition are:
Pendular nystagmus (involuntary eye movement).
Granular appearance of the macula.
Central scotoma (an area of depressed vision and interference in central vision).
3) Generalized Retinal Dystrophies: Both rod and cone photoreceptors are affected in this type. This condition is progressive and severe and can be both syndromic and nonsyndromic. The clinical types are:
Leber Congenital Amaurosis: This is a nonsyndromic type that affects the person during infancy. AIPL1 and CRB1 gene mutations are responsible for this. The clinical presentations are:
Choroideremia: It is nonsyndromic X-linked retinal dystrophy. It is caused by the mutation of the CHM gene and manifests in the second decade of life. The clinical findings are:
What Are the Treatment Options for Retinal Degeneration?
The treatment protocol for retinal dystrophies is difficult to establish because of the involvement of many genes. Modern-day scientists have developed numerous treatment protocols that may cure the disease in various stages.
Gene Therapy: The vector-mediated transduction technique replaces the defective gene in this method. Engineered viral vectors delivering the transgenes for specific retinal cells are injected into the site. Subretinal injections are preferred to deliver the viral vectors into the retinal pigmented epithelium. The subretinal site is chosen as the cell population is static in this area, and the blood-brain barrier provides ocular immune privilege. RPE65 replacement therapy has proved beneficial in patients suffering from Leber congenital amaurosis. However, this therapy is ineffective in advanced cases. Only mild-to-moderate cases with an early diagnosis can be treated using this.
Stem Cell Therapy: Human totipotent cells can be differentiated into various cell types like endodermal, mesodermal, and ectodermal lineages. Embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and retinal progenitor cells (RPC) can be injected into the potential site to replace the defective cells. For ethical reasons, embryonic stem and retinal progenitor cells can not be used for human studies. But induced pluripotent stem cells derived from child or adult fibroblasts have the advantage of increased availability. These cells are derived from an affected individual. There is a reduced risk of host immune system rejection. They are also called human-induced pluripotent stem cells. These cells are seeded on the collagen I matrix, which helps to monolayer sheet of retinal pigmented epithelium. Optical sensors can be used to make these cells functionally stable.
Retinal Prostheses: Gene or stem cell therapy can not be used in advanced cases. For advanced cases, retinal implants or bionic eyes can be used. These electronic devices are inserted into the retina, establishing a neural connection with the brain. Argus II is an approved retinal implant composed of sixty electrodes, a video camera, and a data processing unit.
The application of precision medicine can also be very useful. Clustered, regularly interspaced short palindromic repeats (CRISPR) is a technology through which selected genomic modification of the affected cells can be done.
Retinal degenerative disorders are one of the most dangerous forms of an ocular disorder. These progressive diseases can cause total blindness, and treatment is almost absent in such cases. Recent developments such as gene therapy and stem cell therapy in medicine have provided a ray of hope.