Editorial - Journal of Clinical Ophthalmology (2021) Volume 5, Issue 7
An overview on retinoblastoma: An uncommon eye cancer.
Department of Ophthalmology, University of Lisboa, Lisbon, Portugal
- Corresponding Author:
- Dr. San Arrie
Department of Ophthalmology
University of Lisboa
E-mail: [email protected]
Accepted date: 13 January, 2022
Citation: Arrie S. An Overview on retinoblastoma: An unccommon eye cancer. J Clin Ophthalmol. 2021;5(7):513.
Retinoblastoma is a rare cancer of the infant retina caused by the mutation of both RB1 alleles in a sensitive retinal cell, most likely a cone photoreceptor precursor. When the retinoblastoma protein, pRB, loses its tumour suppressor functions, it causes uncontrolled cell division and recurrent genomic mutations throughout tumour growth. Although pRB is present in almost all tissues, cone precursors have biochemical and molecular characteristics that may make them more vulnerable to RB1 depletion, allowing tumorigenesis. Every year, 8,000 children worldwide are diagnosed with retinoblastoma. Patient survival is greater than 95% in high-income nations, but just 30% globally. However, results are improving as a result of increased awareness for early diagnosis, improved recommendations, and expertise sharing. Intra-arterial and intravitreal chemotherapy have emerged as viable treatments for preserving vision.
Ongoing worldwide collaborations will replace the many categories of eye involvement with uniform criteria in order to reliably analyse treatment choices' eligibility, effectiveness, and safety. Because survivors with heritable retinoblastoma are at danger of getting secondary tumors, they should be monitored for the rest of life. Identifying the molecular consequences of RB1 loss in many organs may lead to novel approaches to the treatment and prevention of retinoblastoma as well as secondary cancers in people with hereditary RB1 mutations.
In underdeveloped nations, orbital extension is a leading cause of mortality in children with retinoblastoma. Poor outcomes are exacerbated by delayed discovery and ineffective care. Conventional treatment, such as primary orbital exenteration, chemotherapy, or radiation, has a death rate of up to 70%. The current awareness of the significance of sequential multimodal therapy with a mix of high-dose chemotherapy, followed by suitable surgery, radiation, and extra adjuvant chemotherapy has significantly improved life salvage.
In developed countries, orbital retinoblastoma is uncommon. In this vast series of 1160 cases gathered over 50 years, Ellsworth reported a gradual drop in the incidence of orbital retinoblastoma. The overall incidence was 8.2 percent from 1925 to 1959 and 7.6 percent from 1959 to 1974. Later, investigators from the same clinic reported that from 1980 to 1986, 6.3 percent (11 of 175) of patients presented with primary orbital retinoblastoma. Although varied, histopathologic evidence of scleral invasion, extrascleral extension, and optic nerve involvement accounts for roughly 2% of cases.
pRB is well recognised as a cell cycle regulator that binds to E2F transcription factors to suppress genes involved in cell proliferation. In response to mitogenic signals, hyperphosphorylation of pRB by Cyclin Dependent Kinases (CDKs) generally reduces repression and promotes the G1 to S phase transition. In the absence of mitogenic signals to allow cell cycle activation, pRB loss alleviates this suppression. It's usually an indication that pRB's primary job is to repress E2F transcription factors, and that loss of this function is the primary cause of retinoblastoma development.
Several "poor penetrance" RB1 mutations encode proteins with little capacity to bind E2F, although these mutations, surprisingly, lead to considerably fewer tumours than RB1 null alleles. As a result, such defective E2F-binding genotypes may significantly inhibit retinoblastoma growth via one or more of pRB's E2F-independent actions. pRB, for example, upregulates p27, which has been linked to cell differentiation, death, and genomic integrity. However, higher pRB expression during cone precursor maturation is related with decreased p27 expression, suggesting that p27 does not mediate retinoblastoma suppression in these cells. The loss of pRB Nterminus activities like as non-homologous end-joining may also be essential, but is not definitely linked to the beginning of retinoblastoma. As a result, the precise method by which pRB typically inhibits retinoblastoma remains unknown.