Retinitis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ilan Dock, B.S.; Jyostna Chouturi, M.B.B.S [2]
Overview
Retinitis refers to the inflammation of the retina as a result of either a genetic disorder or an infectious disease. Genetic disorders are often due to an underlying defect in one of the 50 genes that are necessary for the proper creation of photoreceptor proteins. [1] Progression may therefore be defined by the rate of cellular breakdown of cone and rod cells. Further progression is defined by the degradation of pigment epithelium as well as retinal vessel attenuation and dysfunction of the optic nerve. Infectious diseases may also be responsible for retinitis, as bacterial and viral infections may result in scarring and lesions across the retinal tissue.[2]
Pathophysiology
Genetic Disorders
Retinitis Pigmentosa
- Retinitis pigmentosa is an umbrella term for multiple genetic, retinal disorders.
- Retinal genetic disorders include; night blindness, visual acuity, a fundus appearance, posterior subscapular cataracts, vitreous particle formation, sector retinitis, and pregnancy based retinitis. [3]
- The disease is a result of genetic defects in one of 50 genes required for the proper creation of photoreceptor proteins. [4]
- Generally the genetic disorder is linked to the inheritance of a recessive gene contributed by both parents. [1]
- Other cases have been linked to the inheritance of a dominant gene, defects of the X chromosome, and newly formed mutations caused by diseases.
- Progression of RP causes photoreceptor, cellular breakdown, of both rod and cone cells.
- Ultimately, the progressive breakdown of photoreceptors leads to restricted vision or permanent loss of vision. [1]
Night blindness, Visual acuity, and Fundus appearance
- Night blindness results from the loss of rod cell function in the early portion of the clinical course.
- Visual acuity refers to the loss of central acuity. Progression of visual acuity may be used as an indicator for the severity of the disease's progression.
- Central acuity has been connected to the macular lesions present in the early clinical course of the disease.
- A fundus appearance often refers to the clinical stage.
- Fundus appearance in earlier stages will most often include defective rod cell responses.
- Progression of retinitis will result in the narrowing of the arteriolar portion of the fundus, accompanied by intraretinal pigmentation, and disturbances. These disturbances are often characterized by the degradation of pigments in the pigment epithelium.
- Pigment degradation in the pigment epithelium is an indicator of further degeneration of photoreceptors. This interruption will often manifest in clumping of melanin in odd, coarse configurations.
- Further degradation will result in retinal vessel attenuation and dysfunction of the optic nerve. [3]
Posterior subscapular cataracts, Vitreous particle formation, Sector retinitis, and Pregnancy based retinitis
- Progression of retinitis pigmentosa induces changes in the visual axis of the posterior lens cortex.
- These changes are often described as a yellowish crystalline change, accompanied by colorless, dust-like manifestations.
- Macrophage cells, pigment epithelium, uveal melanocytes, and free melanin pigment granules will mass in the area of dysfunction.
- Other manifestations include pigment epithelial degradation in the form of retinitis punctata albescens and the dysfunction of the optic nerve.
- Severe progression is commonly described as Coats-like disease; a severe case of degradation within the telangiectactic vessels. This particular pathway of progression is commonly attributed to an abnormal amount of lipid deposition in the retina.
- The progression of degradation may be attributed to pathogenic types of CRB1.
- Sector retinitis pigmentosa is often linked to pathogenic variants in the p.Pro 23His of RHO as well as an X-linked variable in heterozygous females.
- These issues will manifest in specific quadrants of the fundus.
- Pregnant women who suffer from retinitis pigmentosa may experience worsened symptoms as physiological changes may occur within the lens and the cornea. [3]
Genetics and Molecular Pathway Defects
- A variety of retinal molecular pathway defects have been matched to multiple known RP gene mutations.
- Mutations in the rhodopsin gene (which is responsible for the majority of autosomal, dominant inherited RP cases) disrupts the process of translating light into decipherable electrical signals within the phototransduction cascade of the central nervous system.
- Defects in the activity of this G-protein-coupled receptor are classified into distinct classes that depend on the specific, abnormal folding and the resulting molecular pathway defects.
- The Class I mutant protein's activity is compromised as specific point mutations in the protein-coding amino acid sequence affect the pigment protein's transportation into the outer segment of the eye, where the phototransduction cascade is localized.
- Additionally, the misfolding of Class II rhodopsin gene mutations disrupts the protein's conjunction with 11-cis-retinal to induce proper chromophore formation.
- Additional mutants in this pigment-encoding gene affect protein stability, disrupt mRNA integrity, and affect the activation rates of the optical proteins, transducin and opsin.[5]
Infectious Agents
Cytomegalovirus
- Retinitis, caused by cytomegalovirus (CMV), involves the infection of all layers of the retinal tissue.
- Spread of the the infection will occur at approximately 24 nanometers per day.
- Primarily infected areas include the RPE and the subjacent choroid.
- Infection will consist of a vast amount of cellular necrosis across the retina; with the enlargement of infected cells, evidently hosting viral inclusions.
- CMV retinitis, post-treatment, will commonly persist on the previously scarred, retinal tissue.
- Progression of infection may result in the development of small holes across previously scarred and healed tissue.
- Formation of these tiny holes may result in rhegmatogenous, retinal detachments. [6]
Ocular Syphilis
- Retinitis resulting from a syphilitic infection is commonly referred to as a ocular syphilis.
- The infection persists as syphilitic spirochetes, Treponema pallidum, that invade or cause allergic reactions within the surrounding tissue.[2]
Endogenous Fungal Infections
- Two types of retinal infections may occur depending on a mode of fungal infection. These two types our outlined as endogenous or exogenous.
- Endogenous fungal retinitis is primarily a result of a disseminated fungal infection.
- Exogenous fungal infections primarily occur as a result of a recently traumatic event such as physical injury or surgery.
- Exogenous fungal infections are usually a result of Candidal retinitis. An infection commonly associated with candida chorioretinitis.
- Candidas chorioretinitis is typically caused by the species Candida albicans.[2]
Tuberculosis
- Extrapulmonary clinical manifestations of tuberculosis include intraocular caseating granulomas.
- Infection of the retina is associated with the spread of the tuberculosis causing bacterial agents.
- Common presentation of tuberculosis in the retina appears as multiple choroidal tubercles.
- These tubercles are best defined as minor nodules with a grayish appearance.[2]
Toxoplasmosis
- Toxoplasma gondii is a parasitic agent found in contaminated meat and egg products.
- Persistence occurs within the vacuoles of cells found within tissues throughout the host.
- Rupturing of tissue cysts within host cells may lead to progression of the disease, ultimately resulting in retinitis. This occurrence is mostly common within individuals who were previously immuno-compromised.[2]
References
- ↑ 1.0 1.1 1.2 Retinitis Pigmentosa. U.S. National Library of Medicine. https://www.nlm.nih.gov/medlineplus/ency/article/001029.htm
- ↑ 2.0 2.1 2.2 2.3 2.4 Infectious Retinitis: A Review. YACHNA AHUJA, MD · STEVEN M. COUCH, MD · RAYMUND R. RAZONABLE, MD · SOPHIE J. BAKRI, MD. http://www.retinalphysician.com/articleviewer.aspx?articleID=102293. Accessed April 13, 2016.
- ↑ 3.0 3.1 3.2 GeneReviews. Retinitis Pigmentosa Overview. 2013; Abigail T Fahim, MD, PhD, Stephen P Daiger, PhD, and Richard G Weleber, MD, DABMG, FACMG. http://www.ncbi.nlm.nih.gov/books/NBK1417/ Accessed April 12, 2016.
- ↑ Retinitis Pigmentosa. U.S. National Library of Medicine. https://www.genome.gov/13514348
- ↑ Mendes HF, van der Spuy J, Chapple JP, Cheetham ME (April 2005). "Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy". Trends in Molecular Medicine. 11: 177–185. doi:10.1016/j.molmed.2005.02.007. PMID 15823756.
- ↑ American Academy of Ophthalmology. Pathophysiology of CMV Retinitis. http://www.aao.org/focalpointssnippetdetail.aspx?id=bc891841-b847-4210-a66b-2bb28d1ef1bf. Accessed April 12, 2016.