Selected predictors of apoptosis in retinitis pigmentosa

The genetics of non syndromic retinitis pigmentosa [RP] is complex with numerous gene mutations. An attempt to overcome each individual mutation provides an overwhelming challenge. However targeting apoptosis which represents a final common pathway to photoreceptor cell death may provide a more practical approach. This study focused on some predictors of apoptosis in RP and their potential usefulness for patients' management and relatives' early diagnosis. Forty nine RP patients with thirty controls were evaluated genetically and ophthalmologicaly with assessment of plasma total nitrite and nitrate [as an index for nitric oxide], Plasma sFas as an index of apoptosis and plasma fatty acids levels. Autosomal recessive RP was the most common type of inheritance and the levels of plasma sFas and nitric oxide [NO] were significantly higher in retinitis pigmentosa compared to controls. Retinitis pigmentosa patients had significantly lower percentage of plasma omega3 fatty acids especially docosahexaenoic acid [DHA] relative to controls. sFas, NO, and DHA could differentiate between RP patients and control subjects with 100%, 100%, 97% sensitivity and 90%, 90%, 100% specificity respectively. sFas and nitric oxide levels were higher in cases of autosomal recessive [AR] type followed by X-linked, autosomal dominant, then simplex cases relative to the control group this may explain why AR and X-Linked forms are clinically more severe. In conclusion; diagnosis and treatment of RP could be aided by systemic markers or predictors of retinal degeneration. The consistent decrease in the plasma omega 3 fatty acids especially DHA, and increase sFas and nitric oxide levels may draw the attention upon the use of these markers as laboratory tests for relatives of affected patients who are at high risk for having retinitis pigmentosa. Also, omega 3 fatty acids in the form of DHA were recommended as possible supplements for the patients and their relatives

P53 expression and histopathological changes in primary and recurrent pterygia among Egyptian cases

The aim of this work is to assess P53 expression and histopathologic features in the epithelia of both primary and recurrent pterygia cases, searching for the pathogenesis of this common lesion. The pterygia specimens from 22 patients [twelve primary and ten recurrent cases] were studied by both routine hematoxylin and eosin stain and immunohistochemically using antibodies against P53 protein. Cases included in this study were 16 males and 6 females. Their ages ranged from 20 to 55 years. Positive family history was recorded in 18.2% of patients and positive parental consanguinity in 9.1% of them. Twenty cases [90.1%] had a history of chronic exposure to solar light i.e prolonged outdoor exposure time [8-12 hours/day] for more than 5 years. Epithelial hyperplasia was more common in recurrent pterygium samples [8 cases] than primary pterygium [only one case]. But, squamous metaplasia with mild dysplasia was more common in Primary pterygium samples [10 cases] than recurrent samples [2 cases]. Ten out of twelve studied specimens with primary pterygium [83.4%] were positive for abnormal P53 expression and two specimens [16.6%] were negative, while only 2 specimens [20%] of recurrent pterygium showed the abnormal positive expression and 8 cases [80%] were negative. Cases with marked and moderate P53 immunostaining [12 cases] showed squamous metaplasia with mild dysplastic changes, nine out of ten cases with negative immunostaining showed epithelial hyperplasia and the remaining sample showed squamous metaplasia without dysplasia. P53 protein is expressed at a high rate in primary pterygia as compared to cases of recurrence. Hence the possible role of P53 in the original development of pterygium, suggesting that pterygium could be a result of uncontrolled cell proliferation and unregulated cell apoptosis which can be proposed a type of benign tumour or even a precancerous condition and not as a degenerative lesion. It seems to be no correlation between P53 expression and recurrence. Recurrent pterygium was related to hyperplastic changes and this may explain the pathogenesis of recurrence especially if the pterygium was not excised completely and the remained epithelial cells continued to grow and formed a new pterygium

study of p53 protein and DNA ploidy in retinoblastoma

Retinoblastoma is the most common primary intraocular cancer in children. It arises from cells that are defective in both copies of the retinoblastoma susceptibility gene [RB I]. Loss of both RB1 and p53 functions may be required for cell immortalization and tumor development. The pattern of p53 expression in retinoblastoma appears to depend on the state of differentiation of the tumor. p53 and RB pocket proteins are important to control DNA ploidy, which may have a value in estimating the prognosis of retinoblastoma. The aim of this work was to assess p53 expression, DNA ploidy, and their relations with histopathologic features in retinoblastoma cases. The study was done on eight patients with retinoblastoma [seven males and one female]. Personal and family history with pedigree analysis were done for all cases. Ophthalmic examination with follow up of tumor regression rate during therapy was performed. Eight primary retinoblastoma samples were obtained from enucleated eyes of all patients. Retinoblastoma sections were stained by hematoxylin and eosin stain and scoring of histopathologic features was performed. Sections were immunohistochemically stained for the protein product of the tumor suppressor gene p53 and quantified for the extent and intensity of the staining. DNA ploidy was examined by assessment of type of DNA histogram and DNA index using cytometric analysis system [CAS 200] after feulgen staining. The proliferative activity was automatically expressed by the CAS 200 as the percentage of cells engaged in the S-phase of the cycle. Our results indicated that p53 protein was immunohistochemically detectable in most retinoblastoma cases [7/8 cases], and was only negative in one case. DNA was aneuploid in 6 out of 8 cases, while 2 cases [one of them was p53 negative, and the other showed weak positivity] were diploid with high proliferative activity. Histopathologic examination revealed that 3 cases were poorly differentiated and 5 cases showed intermediate differentiation with increased necrotic changes and mitotic figures. Retinoblastoma samples showed high degree of p53 protein expression and high degree of aneuploidy which were related to the aggressiveness of histopathologic changes of retinoblastoma. Thus both p53 expression and DNA ploidy have been shown to be markers of aggressiveness of tumor behaviour in retinoblastoma and can help in the prediction of its prognosis

Egyptian study of a rare autosomal dominant bilateral persistent hyperplastic primary vitreous

Persistent hyperplastic primary vitreous [PHPV] is an idiopathic congenital malformation confined to the eye that has no obvious cause and that is usually unilateral and sporadic. The clinical features of the classic PHPV syndrome include white, vascularized tissue covering some or all of the posterior surface of the lens; centrally dragged ciliary processes; secondary glaucoma caused by swelling of the lens or caused by contracture of the retrolental tissue, with anterior shifting of the lens-iris diaphragm; extensive intravitrael hemorrhaging; persistence of the hyaloid artery; and occasionally retinal detachment. In the present study we describe a patient with bilateral PHPV unassociated with other diseases. A normal milestone of development was reported. Family pedigree analysis revealed similarly affected father, grandfather, 2 aunts, 1 uncle from paternal side, also a grand uncle with 2 affected daughters. On examination; height, weight, skull circumference were in 5[th] percentile. Bilateral B and A eye scan ultrasonography for both the patient and the father revealed picture suggestive of persistent hyperplastic primary vitreous. Cytogenetics study by conventional culture technique using CTG banding technique revealed normal male karyotype [46, XY] for both of them. Review of London Dysmorphology Data Base [LDDB], OMIM, and recent medical literature revealed that this case to our knowledge represents the second report supporting autosomal dominant inheritance of PHPV unassociated with other anomalies

Clinical spectrum associated with some structural cerebellar abnormalities

To review the clinical, neuroimaging, cytogenetic, and biochemical studies obtained in 20 patients with different cerebellar structural abnormalities presenting at variable ages of onset with variable signs and symptoms. These patients visited the Clinical Genetics Department, National Research Center, Cairo, Egypt during the period from September 2002 to September 2003. All patients were subjected to complete personal and family history taking 3 generation family pedigree construction and full clinical examination, including complete eye evaluation. Metabolic screening, chromosomal examination and brain CT or MRI, or both, were also carried out. Patients with cerebellar structural abnormalities were broadly divided into those with cerebellar hypoplasia [15 patients; 75%], cerebellar atrophy [3 patients; 15%] and cerebellar white matter abnormalities [2 patients; 10%]. Further, cerebellar hypoplasia was subdivided into cerebello-vermal hypoplasia [4 patients; 20%], vermal-cerebellar hypoplasia [3 patients; 15%] and associated with involvement of other features such as brain stem [4 patients; 20%], posterior fossa [1 patient; 5%]; and intracranial calcification [3 patients; 15%]. This study showed that the type of cerebellar structural abnormality is not the main determining factor of the clinical outcome, but rather the underlying etiology. A high incidence of mostly autosomal-recessive inheritance was diagnosed in 65% of the patients with cerebellar structural abnormalities. Nevertheless, the high rate of consanguinity [18 cases; 90%] with mean inbreeding coefficient of 0.05312 and the similarly affected sibs highlights the role of the autosomal recessive gene in our country

Genetic and environmental factors in different types of age-related cataract among Egyptians

The present study included 280 patients with age-related cataract [153 males and 127 females] and 296 controls with similar age and sex distribution. All cases and controls were subjected to thorough personal and family history taking including consanguinity, occupation, residency, diabetes mellitus, hypertension, smoking, family history of age-related cataract and family pedigree analysis. Full clinical examination also included complete ophthalmological evaluation to determine the type of cataract using slit-lamp examination and visual acuity measurement. Seventy-five patients and 25 controls were subjected to the following investigations: Estimation of serum total protein, serum albumin and globulin levels, albumin/globulin [A/G] ratio, hemoglobin [Hb] level and red blood cells [RBCs] count. Statistical analysis was conducted using SPSS program for calculating t test, X2 test and multiple logistic regression analysis. The present study revealed that mixed cataract [i.e. presence of more than one type of cataract] was the commonest type of age-related cataract in Egypt [48.9% of cases]. Positive family history, consanguinity and exposure to ultraviolet irradiation were universal risk factors for all types of cataract among Egyptians. Diabetes mellitus was associated with nuclear and posterior subcapsular types of cataract, while hypertension had its effect on both cortical and posterior subcapsular types. Biochemical analysis revealed that the risk of age-related cataract increases with decreased level of serum total protein, decreased serum albumin and globulin levels, decreased RBCs count and hemoglobin level

Ocular and electro - ophthalmological studies in Egyptian patients with phenylketonuria

Ocular and electro-ophthalmologic abnormalities are common findings in phenylketonuria [PKU]. The aim of the present work was to study these changes associated with phenylketonuria; also in correlation to magnetic resonance imaging of the brain [MRI], intelligence quotient [IQ] and metabolic control [plasma phenylalanine level]. In addition, the study aimed to test the validity of visual evoked potential [VEP] as an early indicator of metabolic status. The present study was conducted on 20 patients [15 males and 5 females] presenting with phenylketonuria. The patients were subjected to complete history taking including dietary history and three-generation family pedigree analysis. Full clinical examination with complete eye evaluation including eye motility, anterior chamber and fundus examination was done. Electro-retinography [ERG] and VEP studies were performed for all patients. IQ assessment, serum phenylalanine levels evaluation, interictal electroencephalogram assessment [EEG] and MRI were performed. Statistical analysis of the data was done using Student t test

Genetic and biochemical aspects of retinitis pigmentosa among Egyptians

Retinitis pigmentosa is a group of inherited disorders of the retina that are characterized by constriction of the visual fields, night blindness, and fundus changes. Polyunsaturated fatty acids especially omega 3 fatty acid docosahexaenoic acid [DHA] is found in high concentration in the rod outer segment membranes of the retina. The aim of the present study is to evaluate the genetic aspects of retinitis pigmentosa among Egyptian patients in relation to fatty acids. Also to evaluate the associated ocular, systemic, and cytogenetic abnormalities aiming to give a proper genetic counseling. We examined 49 patients that attended the Research Institute of Ophthalmology seeking advice in loss of dark adaptation due to retinitis pigmentosa. Patients under study were submitted to full history taking, family pedigree construction, complete clinical and ophthalmic evaluation, cytogenetic studies and biochemical tests to determine plasma level of omega 3 fatty acids, malondialdehyde, and vitamin E. Retinitis pigmnentosa patients were classified into two groups: Primary retinitis pigmentosa group [93.9%], this group included autosomal recessive retinitis pigmentosa [47.8%], autosomal dominant retinitis pigmentosa [13%], X-linked retinitis pigmentosa [8.7%],and sporadic cases [30.5%], and secondary retinitis pigmnentosa group [6.1%], which included 3 male patients with Usher syndrome type I. Our study showed that autosomal recessive variant of retinitis pigmentosa is the most common and severest type in our country with a high rate of consanguinity [91%], so avoid consanguineous marriage may play an important role in preventing this type of retinitis pigmentosa in our society. Cytogenetic analysis for our patients revealed normal chromosomal complement in all patients with different types of retinitis pigmentosa apart from gap in chromosome 6q [chromatic gap] which was reported in 5/20 [25%] of metaphases studied in a male patient presented with autosomal recessive retinitis pigmentosa. Decrease plasma level of vitamin E, and increase plasma level of malondialdehyde was noticed in autosomal dominant and sporadic types of retinitis pigmentosa patients. Consistent decrease in the plasma omega 3 fatty acids especially docosahexaenoic acid [DHA], which was found in most patients with retinitis pigmentosa, may draw the attention upon the use of omega 3 blood level as a laboratory test for relatives of affected patients who are at high risk of having early stages of retinitis pigmentosa. We recommend DHA, and vitamin E supplement for those patients with decrease plasma level of omega 3 fatty acids

Heritability of strabismus among Egyptian population

The etiology of strabismus has long been observed to have a genetic component. Since strabismus is one of the major causes of an amblyobia, early detection and treatment is essential for restoration of proper alignment of the visual axes and establishment of binocular vision. We examined 100 patients with strabismus, 50 males and 50 females, attending the Research Institute of Ophthalmology, aiming to study the heritability and different factors predispose to strabismus for early intervention. Patients under study were submitted to full history taking, family pedigree construction, complete clinical examination, including eye evaluation, and cytogenetic study of the peripheral blood lymphocytes when indicated. Patients with strabismus were classified into two groups. The first group included 76 patients with esotropia [76%], winch subclassified into two groups: Isolated group [72%], included 66 patients with infantile esotropia [66%], 5 patients with Duane syndrome [5%], and 1 patient with congenital ocular fibrosis [1%]. And associated group [strabismus is a component of a genetic syndrome] which included 4 [4%] patients with Mobius syndrome. The second group included 24 [24%] patients with isolated exotropia. Our study revealed that heritability plays an important role in development of strabismus. Also low birth weight is an important risk factor. So young infants in families at high risk for developing strabismus, and low birth weight infants should be screened for early detection, better intervention and therapeutic trials, this allow normal development of binocular vision, depth perception, and prevent psychosocial dysfunction. There is limited evidence in support of an environmental causes of strabismus