Major Cause Of Childhood Blindness Research Articles

Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a clinically multifactorial process characterized by the aberrant vascularization of the retina that has potentially devastating effects on vision in preterm infants. Despite an appreciation for the postnatal risk factors that contribute to the development of ROP, this condition continues to be a major cause of childhood blindness. Studies using the mouse model of oxygen-induced retinopathy (OIR) have identified new therapeutic targets that may be used to guide treatment and determine which babies are at highest risk for ROP development. Such factors include the hypoxia-driven proteins vascular endothelial growth factor (VEGF) and erythropoietin (EPO) as well as the maternally derived factors insulin-like growth factor-1 (IGF-1) and omega-3 polyunsaturated fatty acids (PUFAs). Each has been demonstrated to have phase-specific effects on the pathogenesis of ROP. Through an understanding of the contribution of the IGF-1 pathway to the development of ROP in particular, a new algorithm has been developed (WINROP™) that uses postnatal weight gain to identify infants at highest risk for ROP in an attempt to target therapy and resources more effectively.

Biochemical and structural properties of four CYP1B1 mutations present in primary congenital glaucoma (PCG) patients

Methods: The study involves heterologous protein expression of four mutant CYP1B1 forms (Y81N, E229K, A330F, R368H) in E. coli, analyzing their stability and ability to metabolize the endogenous substrates, estradiol, arachidonic acid and retinoids.Results: PCG is a major cause of childhood blindness and occurs due to an abnormal development of the trabecular meshwork (TM) and anterior chamber region of the eye. Our group was the first to link mutations in the CYP1B1 gene to the PCG phenotype. The role of CYP1B1 in eye development may involve its oxidative metabolic activity, whereby it could either generate or degrade an active signaling molecule, e.g. a morphogen, which affects the downstream transcriptional expression of genes associated with proper eye development. The data showed a high degree of instability for the Y81N and E229K mutant proteins. All the four mutants affected the metabolic activity significantly. The results were correlated with the structural changes in the CYP1B1 protein due to amino acid substitutions, based upon CYP1A2 crystal structure.Conclusion: The findings suggest that altered enzymatic properties of the CYP1B1 mutants towards endogenous substrates may be the cause of impaired eye development and the PCG phenotype.(Support: NIH grants R01 EY11095, 5R03 EY014654; American Health Assistance Foundation award AHAF G2007‐036)

Genetic susceptibility to retinopathy of prematurity: the evidence from clinical and experimental animal studies

Despite advances in management and treatment, retinopathy of prematurity remains a major cause of childhood blindness. Evidence for a genetic basis for susceptibility to retinopathy of prematurity is examined, including...

Purification, characterisation and intracellular localisation of aryl hydrocarbon interacting protein-like 1 (AIPL1) and effects of mutations associated with inherited retinal dystrophies.

Mutations in AIPL1 are associated with Leber Congenital Amaurosis (LCA), a major cause of childhood blindness, yet the cellular function of the encoded protein has yet to be fully elucidated. In order to investigate the biochemistry of AIPL1, we have developed a system for the expression of the recombinant protein in bacteria and its subsequent purification. The secondary structure and thermostability of wild-type and mutant proteins have been examined by circular dichroism (CD) spectroscopy. Some of the variants, notably W278X and P376S, had markedly different secondary structure compositions, indicating that the proteins had not folded properly, whilst W278X and T114I were particularly thermolabile. When eukaryotic cells were transfected with the AIPL1 expression constructs, we show by immunofluorescence microscopy that wild-type protein is distributed throughout the nucleus and cytoplasm. Several of the mutants give similar results. With two of the disease-associated variants (W278X and A336Delta2), however, the protein remains in the cytoplasm in aggresome-like particles. These particles were shown to be ubiquitinated, indicating that the mutant protein had been tagged for proteosomal degradation. On this basis, we can conclude that wild-type protein is expressed in a soluble and folded manner, and that some of the disease-associated mutant proteins are nonfunctional because they are insoluble and are degraded by the cell. Other mutations appear to have a more localised effect on secondary structure, which does not result in insolubility or affect protein targeting, but reduces the stability of the protein at human body temperature.

Hereditary disease as a cause of childhood blindness: regional variation. Results of blind school studies undertaken in countries of Latin America, Asia and Africa.

There is evidence from developed countries that genetic disease is the major cause of childhood blindness. Little data are available from most developing and newly industrialised countries concerning the relative importance of hereditary diseases as a cause of childhood blindness. Children in schools for the blind in 13 countries of Africa, Latin America and Asia were examined between 1990 and 1994 using a standardised method The anatomical site of abnormality and underlying aetiology were analysed for children with a corrected acuity in the better eye of less than 6/60 (severe visual impairment and blindness, svi/BL). In these countries II-39% of svi/BL was attributed to genetic disease. Genetic diseases were responsible for a higher proportion of childhood visual loss in countries with higher levels of socio-economic development. An autosomal recessive mode of inheritance was reported in 22-52% of children with genetic disease. Retinal dystrophies were the commonest form of genetic eye disease (49-80%) in all countries apart from Thailand and the Philippines where cataract was the commonest (43.9%). The role of consanguinity, and opportunities for further research are discussed.

Detection of ocular surface abnormalities in experimental vitamin A deficiency.

Hypovitaminosis A is the major cause of childhood blindness in many developing countries. Unfortunately, serum vitamin A levels do not accurately reflect liver stores, and there is no good objective test for detecting early, physiologically important deficiency. The purpose of this study was to determine if we could detect ocular surface abnormalities in the eyes of vitamin A-deficient rabbits at early stages of xerophthalmia. Cellulose acetate filter strip impressions were taken serially from the bulbar conjunctiva of vitamin A-deficient rabbits every two weeks, beginning eight to 12 weeks before keratinization of the corneal or conjunctival epithelium was clinically apparent. The percentage of light microscopic fields containing goblet cells decreased, and the percentage of fields containing enlarged epithelial cells increased in a linear fashion, beginning at least four to six weeks before the clinical changes. The results indicate that this technique may be of potential usefulness as a screening tool for early xerophthalmia.

Life changes as etiologic factors in juvenile rheumatoid arthritis

JUVENILE Rheumatoid Arthritis (JRA or Still's Disease) is significant disease of children, annually affecting 175,000 (1 in 1,500) children in this country [1]. It cripples more children than any other musculo-skeletal disease and is major cause of childhood blindness [2]. Great strides have been made in diagnosis, treatment, and management of JRA, yet its etiology remains obscure. Immunopathy, allergy, infection, trauma, heredity, and psychosocial factors have all been postulated, but no conclusion has been reached. In focusing upon psychological factors involved, author agrees with Scotch and Geiger [3] who assume JRA may have a multiple, rather than unitary etiology .... The question is not whether social factors 'cause' disease, but rather whether they contribute to its causation. Although there was and is controversy, JRA is generally regarded as variant of Rheumatoid Arthritis (RA) [2-5], and despite significant differences in natural history of disease [2, 6], literature concerning both RA and JRA and their relationship to psychosocial factors will be reviewed briefly. A link between psyche and soma in RA has been hypothesized since 1920's [7-10]. However, no clear cut evidence such as Engel's [11] classic work with ulcerative colitis has emerged. Most investigations have concentrated on personality analysis and behavior patterns. King [7] described RA patient as shy and socially inadequate, self-sacrificing, overconscientious, depressed, and unable to show hostility. Later, he and Cobb [12] associated RA with men who made less money, had terminated marriages, worried more, and had fewer children; in women who had less education and more children; and in both sexes where there was incongruity of income and education. Cormier and Wittkower [13] say that RA patients have difficulty in usual methods of coping with environment and with other people, and severe blocking of external expression of emotion with internalization of feeling and autonomic activity. Solomon [14], comparing 16 RA patients with their unaffected siblings by means of psychodrama, noted that no RA showed more anger than sibling, and only 2 showed as much. He states that the clearest and most consistent finding related to masochism, self-sacrifice, and denial of hostility shown by arthritic patients. With Moos [15], he administered MMPI to patients and siblings and showed that RA's had higher scores on somatic reaction, female masochism, psychological rigidity and moralism, complianee/subserviance, reserve/introversion, and conservatism/security.

Finding children with blindness and visual impairment in five local government areas of Sokoto state using the key informant method

Background: Pilot inclusive education program that provide education to blind children in routine schools have been implemented in 1 local government area (LGA) of Sokoto state in 2009. Encouraged by the success recorded in the initiative, the Sokoto state Ministry of Education through the State Universal Basic Education Board (SUBEB) decided to expand the programme to other LGAs across the three senatorial districts. This study was conducted to trace blind/visually-impaired children in 5 LGAs of the state in order to link them with clinical, educational or rehabilitative services. Materials and Methods: Primary health care workers (PHCWs) and volunteers were used as key informants over a 10-day period to trace visually impaired/blind and bring them to an examination venue. This followed mobilization and sensitization of the community leaders. A team of an ophthalmologist, optometrist and ophthalmic nurse conducted the eye examination in each LGA on a fixed date including refraction. Results: A total of 107 children were reviewed as children having eye problems. Girls constituted 45% of the children. Twenty-seven children (25%) were found blind using a VA of Conclusion: The major causes of childhood blindness in Sokoto state are either preventable or curable.