Biomedical subjects

Itay Chowers

Publications and source records attributed to Itay Chowers.

At least 19 recordsLinked to original sources

PubMed2006

Application of the standard photodynamic treatment protocol for symptomatic circumscribed choroidal hemangioma.

PURPOSE: To describe the results of photodynamic therapy (PDT) using a standard protocol, developed for treating choroidal neovascularization (CNV), for the treatment of circumscribed choroidal hemangioma (CCH). METHODS: A prospective, uncontrolled, consecutive case series of patients with symptomatic CCH that were treated using the standard PDT protocol was evaluated periodically with ophthalmic exams and echography. RESULTS: Nine CCH patients were included in the study. Mean tumor height decreased from 2.7 mm before treatment to 0.8 mm at the end of the follow-up period. Mean visual acuity improved from 6/15 to 6/12. Six patients required one PDT session, two patients two sessions, and one patient three sessions. Side effects included transient visual disturbances in two patients. One patient, who concomitantly presented with age-related macular degeneration, developed CNV. CONCLUSIONS: The standard PDT protocol is effective for the treatment of CCH. Complications are uncommon. Further studies should assess the optimal PDT protocol for the treatment of CCH.

Adult↗

PubMed2006

The iron carrier transferrin is upregulated in retinas from patients with age-related macular degeneration.

PURPOSE: Iron can cause oxidative stress, and elevated iron levels have been associated with several neurodegenerative diseases including age-related macular degeneration (AMD). Transferrin, an iron transport protein, is expressed at high levels in the retina. The purpose of this study was to assess transferrin involvement in AMD by determining the expression profile of transferrin in retinas with AMD compared with retinas without evidence of disease. METHODS: Postmortem retinas were obtained from AMD and non-AMD eyes. Expression of transferrin was assessed in a microarray dataset from 33 retinas of unaffected donors and 12 retinas of patients with AMD (six with neovascular AMD and six with non-neovascular AMD). Quantitative real-time RT-PCR (QPCR) was used to confirm the microarray results. Transferrin protein expression was assessed by semiquantitative Western blot analysis and immunohistochemistry. RESULTS: In comparison to unaffected retinas, mean transferrin mRNA levels, as measured by microarray analysis were elevated 3.5- and 2.1-fold in non-neovascular and neovascular AMD retinas, respectively. Semiquantitative Western blot analysis demonstrated a 2.1-fold increase in transferrin protein in AMD eyes. Immunohistochemistry showed more intense and widespread transferrin label in AMD maculas, particularly in large drusen, Müller cells, and photoreceptors. CONCLUSIONS: These data demonstrate that transferrin expression is increased in the retinas of patients with AMD relative to those of healthy control patients of comparable age. Along with previous studies that have demonstrated elevated iron levels in AMD retinas, early onset drusen formation in a patient with retinal iron overload resulting from aceruloplasminemia, and retinal degeneration with some features of macular degeneration in the iron-overloaded retinas of ceruloplasmin/hephestin knockout mice, the present study suggests that altered iron homeostasis is associated with AMD.

Adult↗

PubMed2005

Identification of regulatory targets of tissue-specific transcription factors: application to retina-specific gene regulation.

Identification of tissue-specific gene regulatory networks can yield insights into the molecular basis of a tissue's development, function and pathology. Here, we present a computational approach designed to identify potential regulatory target genes of photoreceptor cell-specific transcription factors (TFs). The approach is based on the hypothesis that genes related to the retina in terms of expression, disease and/or function are more likely to be the targets of retina-specific TFs than other genes. A list of genes that are preferentially expressed in retina was obtained by integrating expressed sequence tag, SAGE and microarray datasets. The regulatory targets of retina-specific TFs are enriched in this set of retina-related genes. A Bayesian approach was employed to integrate information about binding site location relative to a gene's transcription start site. Our method was applied to three retina-specific TFs, CRX, NRL and NR2E3, and a number of potential targets were predicted. To experimentally assess the validity of the bioinformatic predictions, mobility shift, transient transfection and chromatin immunoprecipitation assays were performed with five predicted CRX targets, and the results were suggestive of CRX regulation in 5/5, 3/5 and 4/5 cases, respectively. Together, these experiments strongly suggest that RP1, GUCY2D, ABCA4 are novel targets of CRX.

Animals↗

PubMed2005

T1799A BRAF mutations in conjunctival melanocytic lesions.

PURPOSE: To gain a better understanding of the molecular events leading to the development of conjunctival melanocytic lesions and conjunctival melanoma, this study was conducted to investigate the presence of T1799A BRAF oncogenic mutation in these lesions. METHODS: Forty-eight surgically excised conjunctival melanocytic lesions from 48 patients were examined for the presence of the BRAF T1799A mutation. Twenty-eight lesions were conjunctival nevi, of which 20 were excised from children younger than 18 years. Fifteen lesions were conjunctival primary acquired melanosis (PAM; 11 without atypia and 4 with atypia) and five were conjunctival melanomas. To detect the BRAF T1799A mutation, both a newly developed kit (Mutector; TrimGen, Sparks, MD) and direct DNA sequence analysis of exon 15 after PCR amplification were used. RESULTS: The T1799A BRAF mutation was identified in 14 of 28 (50%) conjunctival nevi analyzed, but in none of the 15 conjunctival PAMs, with and without atypia. The T1799A BRAF mutation was identified in two of the five (40%) conjunctival melanomas. There was no difference in the BRAF mutation detected in conjunctival nevi in children or adults, as the BRAF mutation was detected in 50%. CONCLUSIONS: The results showed that conjunctival nevi, similar to skin nevi, have a high frequency of oncogenic BRAF mutations. Furthermore, the results suggest that the oncogenic event leading to BRAF mutations affect only conjunctival nevi and not conjunctival PAM. The clinical significance of these observations remains to be determined.

Adolescent↗

PubMed2004

Comparative gene expression analysis of murine retina and brain.

PURPOSE: Several high-throughput studies have described gene expression in the central nervous system (CNS), and recently there has been increasing interest in analyzing how gene expression compares in different regions of the CNS. As the retina is often used as a model system to study CNS development and function, we compared retina and brain gene expression using microarray analyses. METHODS: Mouse retina, brain and liver RNA was hybridized to a custom cDNA microarray containing 5,376 genes and ESTs, and the data from the quantified scanned images were analyzed using Bioconductor and SAM. Preferential retina expression was confirmed by real-time PCR. The cellular distribution of genes newly identified as retina enriched genes was determined by immunohistochemistry. RESULTS: Using stringent statistical analyses we identified 733 genes that were preferentially expressed in retina and 389 in brain. The retina-liver hybridizations identified an additional 837 retina enriched genes. The cellular distribution in the retina was determined for two genes that had not previously been reported to be expressed in the retina, the transcription regulatory proteins EWS and PCPB1. Both proteins were found primarily in the inner nuclear layer. Finally, a comparison of the microarray data to publicly available SAGE and EST library databases demonstrated only limited overlap of the sets of retina enriched genes identified by the different methodologies. The preferential retinal expression of a subset of genes from the microarray, which were not identified as differentially expressed by other methods, was confirmed by quantitative PCR. CONCLUSIONS: The finding of differences in the groups of identified retina enriched genes from the various profiling techniques supports the use of multiple approaches to obtain a more complete description of retinal gene expression. Characterization of gene expression profiles of retina and brain may facilitate the understanding of the processes that underlie differences between the retina and other parts of the central nervous system.

Animals↗

PubMed2004

Changes in retinal pigment epithelial gene expression induced by rod outer segment uptake.

PURPOSE: Rod outer segment (ROS) uptake, a crucial function of the retinal pigment epithelium (RPE), probably involve multiple proteins, yet only a small number have so far been identified. The goal of this study was to find additional genes involved in ROS uptake and degradation by identifying ROS-induced gene expression changes. METHODS: Human RPE-derived ARPE-19 cells were harvested 3 and 12 hours after addition of bovine ROS. Gene expression profiles were compared with control cultures by using a custom human retina cDNA microarray and were validated by quantitative real-time RT-PCR (QPCR). ROS binding and internalization were quantitated with a fluorescence assay. RESULTS: Alterations in the expression levels of multiple genes (especially ones involved in transcriptional regulation, signal transduction, or protein modification) were detected 3 hours after ROS challenge, whereas by 12 hours most had returned to baseline. QPCR results corroborated the microarray results for seven of the eight genes tested. Time-course QPCR experiments on an independent sample set demonstrated characteristic temporal expression changes for each gene. Protein levels of one of these, plasminogen activator inhibitor-1 (PAI-1), were tested and found to parallel the mRNA changes. In addition, exogenous PAI-1 inhibited ROS uptake by RPE cells in vitro, consistent with its putative function in integrin receptor regulation. CONCLUSIONS: ROS uptake is associated with regulation of multiple RPE genes in a gene-specific temporal pattern. These genes are candidates for involvement in ROS uptake and degradation, particularly PAI-1, for which the study provided evidence suggesting that it may participate in the negative feedback of ROS uptake.

Animals↗

PubMed2004

Increased expression of iron-regulating genes in monkey and human glaucoma.

PURPOSE: To understand the mechanisms mediating retinal ganglion cell loss in glaucoma, the gene expression patterns were compared for transferrin, ceruloplasmin, and ferritin between normal and glaucomatous retina in monkey and human eyes. METHODS: Laser photocoagulation was used to produce unilateral experimental glaucoma in monkeys. Gene expression was assessed by in situ hybridization and quantitative reverse transcription polymerase chain reaction (PCR). Immunohistochemistry was used to examine the retinal expression of iron-related proteins in the retina in experimental monkey glaucoma and human glaucoma. RESULTS: Comparison of glaucomatous with control monkey retinas demonstrated increased mRNA expression of transferrin, ceruloplasmin, and ferritin heavy and light chains. In situ hybridization localized retinal gene expression of transferrin mainly to the inner nuclear layer and ferritin to both the inner and outer nuclear layers. Immunohistochemical examination of monkey and human glaucoma for these iron-related proteins demonstrated increases at the protein level. CONCLUSIONS: Increased mRNA and protein levels of the iron-regulating proteins transferrin, ceruloplasmin, and ferritin are present in glaucoma. Together, these results suggest the involvement of iron and copper metabolism and associated antioxidant systems in the pathogenesis of glaucoma.

Aged↗

PubMed2004

Identification of gene expression changes associated with the progression of retinal degeneration in the rd1 mouse.

PURPOSE: One approach to gaining insight into the biological pathways contributing to rod and cone photoreceptor death is to identify patterns of gene expression changes. In the present study, a custom retinal microarray was developed to analyze the rd1 mouse, a well-characterized animal model of human retinal degeneration. METHODS: A microarray was constructed containing cDNA fragments corresponding to genes known or postulated to be involved in normal retinal function, development, and disease. Gene expression in rd1 retina was compared with age-matched control retinas at three time points: the peak of rod degeneration (postnatal day [P]14), early in cone degeneration (P35), and during cone degeneration (P50). Selected microarray results were confirmed with real-time PCR. The cellular distribution of one of the differentially expressed genes, dickkopf 3 (Dkk3), was assessed by in situ hybridization. RESULTS: At each stage of degeneration, there was only limited overlap of the genes that showed increased expression, suggesting the involvement of temporally distinct molecular pathways. Genes active in transport mechanisms and in signaling pathways were differentially expressed during rod degeneration, whereas genes with functions in protein modification and cellular metabolism were differentially expressed during cone degeneration. Increased expression of genes involved in cell proliferation pathways and oxidative stress was observed at each time point. CONCLUSIONS: These microarray results provide clues to understanding the molecular pathways underlying photoreceptor degeneration and indicate directions for future studies. In addition, comparisons of normal and degenerated retina identified numerous genes and ESTs that are potentially enriched in rod photoreceptors.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Studies on retinal and retinal pigment epithelial gene expression.

The 'completion' of the murine and human genomes and creation of high-density expressed sequence tag (EST) databases from multiple tissues and multiple species, coupled with the development of high-throughput expression profiling approaches such as microarrays and Serial Analysis of Gene Expression (SAGE), is making possible the in-depth analysis of gene expression patterns in health and disease to an extent that was not previously possible. Such new information is providing insight into normal function, and into how normal function is altered in disease. Efforts have begun, and are accelerating, in the application of expression profiling to the study of the retina and retinal pigment epithelium (RPE). In this chapter we will review progress in this area. We will also discuss technical issues that make expression studies of the RPE particularly challenging, and share our experience in methodological approaches to overcome these challenges.

Animals↗

PubMed2004

[Experimental therapeutic modalities for retinitis pigmentosa].

Retinitis Pigmentosa (RP) is a heterogeneous group of inherited diseases that cause retinal degeneration, often leading to blindness. Over the last decade, significant insights have been obtained into the mechanisms underlying retinal degeneration in RP. This improved understanding of the pathogenesis of RP, combined with advances in molecular and cellular biology methods as well as electro-optical technologies, have contributed to renewed interest and increasing efforts to design novel therapeutic approaches for RP. In the first part of this review (Harefuah, April 2003), we summarized recent developments in the fields of gene therapy for RP, the use of neurotrophic growth factors, and attempts to alter disease progression by vitamins and nutritional modifications. In this second part of the review, retinal and retinal pigment epithelium transplantation, the potential use of stem cells to replace degenerating retinal cells and attempts to develop a retinal prosthesis using electro-optical devices are described. The exciting progress made in these various experimental directions raises hope that slowing or preventing the progression of retinal degeneration in RP patients, and perhaps even partial restoration of visual function in RP, is within reach.

Disease Progression↗

PubMed2003

Gene expression variation in the adult human retina.

Despite evidence that differences in gene expression levels contribute significantly to phenotypic variation across individuals, there has been only limited effort to study gene expression variation in human tissue. To characterize expression variation in the normal human retina, we utilized a custom retinal microarray to analyze 33 normal retinas from 19 donors, aged 29-90 years. Statistical models were designed to separate and quantify biological and technical sources of variation, including age, gender, eye laterality, gene function and age-by-gender interaction. Although the majority of the 9406 genes analyzed showed relatively stable expression levels across different donors (for an average gene the expression level value of 95 out of a 100 individuals fell within a 1.23-fold range), 2.6% of genes showed significant donor-to-donor variation, with a false discovery rate of 10%. The mean expression ratio standard deviation was 0.15+/-0.8, log2, with a range of 0.09-0.99. Genes selectively expressed in photoreceptors showed higher expression variation than other gene classes. Gender, age and other donor-specific factors contributed significantly to the expression variation of multiple genes, and groups of genes with an age- and gender-associated expression pattern were identified. Our findings show that a significant fraction of gene expression variation in the normal human retina is attributable to identifiable biological factors. The greater expression variability of many genes central to retinal function (including photoreceptor-specific genes) may be partially explained by the dynamics of the vision process, and raises the possibility that photoreceptor gene expression levels may contribute to phenotypic diversity across normal adult retinas. In addition, as such diversity may result in different levels of disease susceptibility, exploring its sources may provide insights into the pathogenesis of retinal disease.

Adult↗

PubMed2003

Retinal function abnormalities in patients treated with vigabatrin.

OBJECTIVE: To evaluate central and peripheral retinal function in patients treated with vigabatrin, an antiepileptic drug associated with peripheral visual field constriction (VFC). METHODS: Six patients with epilepsy treated with vigabatrin as add-on therapy for at least 3 years were included in this observational case series. All patients underwent a clinical ophthalmologic examination, color vision testing, standard perimetry, and full-field and focal foveal cone electroretinography. Four patients, 3 of whom had VFC, completed specialized computerized static light- and dark-adapted perimetry. RESULTS: In 9 of 11 eyes tested, foveal cone electroretinographic amplitudes were at or below the lower limit of normal. Dark-adapted perimetry demonstrated abnormal rod-derived visual fields in the 3 patients with vigabatrin-attributed VFC, whereas rod-derived thresholds were within normal limits throughout the visual field in the patient who did not have VFC. CONCLUSIONS: Our results suggest that vigabatrin not only impairs peripheral cone-derived function as manifested by VFC but also affects foveal cone electroretinographic amplitudes and rod-derived visual fields. The clinical dilemma regarding the use of vigabatrin therapy is further complicated since central as well as peripheral visual function seems to be adversely affected.

Adolescent↗

PubMed2003

Gene delivery by viral vectors in primary cultures of lacrimal gland tissue.

PURPOSE: To test the feasibility of gene transfer into lacrimal gland tissue in primary culture, using different viral vectors. METHODS: Lacrimal glands were dissected from adult Sabra rats and divided by pincers to 0.3-0.4 mm fragments. Tissue was maintained under primary organ culture conditions using the "raft" technique. The ability of three different viral vectors to conduct beta-galactosidase (beta-gal) gene delivery was examined: adenovirus (Ad5CMVLacZ), vaccinia (VSC9), and herpesvirus (tkLTRZ(1)). Tissue fragments were incubated for 60 minutes with one of the viral vectors and transferred to fresh medium. After 3 and 7 days, beta-gal expression was examined by X-gal staining in gross preparations and in histologic sections. RESULTS: At 3 days, beta-gal expression was observed in 33% of tissue fragments exposed to the vaccinia vector and in 18% and 14% of fragments exposed to the adenoviral and herpes vectors, respectively. After 7 days in culture, successful gene delivery occurred in 77% of vaccinia, 41% of adenovirus, and only 13% of herpesvirus applications. Vector-specific reporter gene expression patterns were observed: With the vaccinia vector, lacrimal duct cells were predominantly stained; in contrast, the adenoviral vector tended to transduce the interacinar areas, with beta-gal expression mainly occurring within the myoepithelial cells. CONCLUSIONS: Vaccinia and adenovirus are efficient vectors for gene transfer into lacrimal gland tissue in primary culture. The specific expression pattern obtained by the vaccinia vector probably reflects its characteristic tissue tropism to lacrimal duct cells. The results presented in this ex vivo system may be a first step toward expressing genes with products that could be continuously delivered to the eye through the tears. Such proteins could include anti-inflammatory, anti-angiogenic, anti-herpetic, anti-bacterial, or anti-glaucomatous agents, among others.

Adenoviridae↗

PubMed2003

Identification of novel genes preferentially expressed in the retina using a custom human retina cDNA microarray.

PURPOSE: To construct a custom cDNA microarray for comprehensive human retinal gene expression profiling and apply it to the identification of genes that are preferentially expressed in the retina. METHODS: A cDNA microarray was constructed based on the predicted human retina gene expression profile according to expressed sequence tag (EST) databases. Gene expression profiles were obtained from five human retinas, two livers, and the cerebral cortical regions of two brains. Each sample was studied in duplicate, using a reference sample experimental design. Retina-enriched genes were identified by using the significance analysis for microarray (SAM) algorithm. Quantitative real time PCR was used to confirm microarray results. Bioinformatic analysis was performed to compare the array results with expression data available from public databases. RESULTS: The cDNA microarray contains 10,034 sequences: 67% represent known genes and 33% represent ESTs. Differential hybridization with the array identified, in addition to known retinal genes, 186 retina-enriched genes that do not have known retinal function. Of these, 96 represent novel genes. Quantitative real-time PCR of 11 of the identified genes and ESTs confirmed their retina-enriched expression pattern. Bioinformatic analysis of EST databases suggests that of the 186 genes, approximately 40% are predominantly expressed in the retina, whereas the remainder show significant expression in other tissues. Comparison of this study's microarray-based retina-enriched gene set with three published similar sets identified using complementary high-throughput approaches demonstrated only limited overlap of the identified genes. CONCLUSIONS: Because previous studies have demonstrated that many retina-enriched genes are crucial for maintaining normal retinal function, the genes identified here are likely to include ones that have important roles in the retina and ones that when mutated can cause or modulate retinal disease. In addition, the retina custom array should provide a useful resource for comparing expression profiles between normal and diseased human retinas.

Adult↗

PubMed2003

Lack of BRAF mutation in primary uveal melanoma.

PURPOSE: BRAF T1796A activating mutations have been found in a high proportion of cutaneous melanomas, cutaneous nevi, and papillary thyroid carcinoma and in a small fraction of other cancers. This study was designed to investigate the incidence of BRAF T1796A mutation in uveal melanoma. METHODS: Twenty-nine formalin-fixed, paraffin-embedded posterior uveal melanomas were included in the study. DNA was extracted from the paraffin sections followed by PCR amplification of exon 15 and detection of the common BRAF missense mutation (T-->A transversion at nucleotide 1796) using restriction enzyme analysis. RESULTS: Although positive cutaneous melanoma control cell lines harbored the T1796A BRAF mutation, none of the 29 uveal melanomas harbored the mutation. CONCLUSIONS: These data suggest that BRAF T1796A activating mutation is not common in primary uveal melanoma. These findings are in accord with known differences in tumorigenesis between uveal and cutaneous melanomas.

DNA Mutational Analysis↗

PubMed2003

[Experimental therapeutic modalities for retinitis pigmentosa].

Retinitis Pigmentosa (RP) is a heterogeneous group of inherited diseases that cause retinal degeneration, often leading to blindness. Over the last decade, the advent of molecular biological techniques has greatly improved our understanding of the genetic and molecular processes underlying these diseases. This has prompted research efforts aimed at the development of novel therapeutic modalities for RP, and the purpose of this review is to present current trends in this field. In this first of two parts, advances in gene therapy, the use of neurotrophic growth factors, and attempts to alter disease progression by vitamins and nutritional modification are discussed. Experimental treatments involving surgical intervention will be addressed in a future, second part of this review that will include the topics of retinal and retinal pigment epithelium transplantation, the potential use of stem cells to replace degenerating retinal cells, and the development of "artificial vision" using electro-optical devices. The encouraging progress made in these various experimental directions lends hope that efficient treatment for at least some of the patients suffering from these blinding diseases is within sight.

Disease Progression↗

PubMed2002

Changes in ultrasound findings in posterior uveal melanoma after Ruthenium 106 brachytherapy.

PURPOSE: To analyze the postbrachytherapy ultrasonographic dynamics of uveal melanoma tumor height and internal reflectivity. DESIGN: Prospective, comparative, observational case series. PARTICIPANTS: One hundred forty-seven patients (147 eyes) with posterior uveal melanoma having a mean age of 61 years (range, 29-97 years) who were treated with Ruthenium 106 brachytherapy. METHODS: Patients were followed-up with ultrasonography using both A and B modes of standardized echography every 6.7 +/- 0.3 months (mean +/- standard error of the mean) for a total of 1001 ultrasound examinations. On average, each patient was examined 5.8 times (range, 3-17 times). The echographic parameters included tumor base size, height, internal reflectivity, regularity, vascularity, and extra-scleral extension. To compare the response of tumors of different sizes, each tumor was standardized to its initial size at brachytherapy. MAIN OUTCOME MEASURES: The dynamics of the tumor height and internal reflectivity. RESULTS: At the time of brachytherapy, the mean height of the tumors was 5.2 mm (range, 2.2-11.8 mm). After brachytherapy, 142 tumors (96.6%) responded by a decrease in height. The decrease in height was at an initial rate of approximately 3% per month. Most of the tumors did not regress entirely; rather, their height stabilized on a constant value (on average 61% of the initial height) after approximately 18 to 24 months. The decrease in height after brachytherapy was best fitted by the sum of a first order exponential decay and a constant (h = 61 + 35*e(-0.12t), in which t = time in months). The half-life of the decay was 5.8 months. Large tumors (>8 mm) had a faster initial decrease in height, and stabilized on a lower percentage of their initial height (50%) compared with small tumors (70%). Thus, the half-life of the height exponential decay was 5.3 months for small tumors (2-4 mm) and 3.3 months for the large tumors (>8 mm). Internal reflectivity increased from a mean of 40% before therapy to 70% after 2 years. The dynamics of the reflectivity were best fitted with the function: f = 45 + 24(1-e(-0.09t)). Larger tumors, which initially had lower internal reflectivity, presented with a slower increase in internal reflectivity (t() = 8.7 months) compared with smaller tumors (t(1/2) = 5 months). CONCLUSIONS: The postbrachytherapy ultrasonographic dynamics of uveal melanomas resemble a function composed of the sum of a constant and a first order exponent, suggesting the possible existence of two components (cell populations), one unaffected by brachytherapy and the other a radiosensitive population that reacts to brachytherapy in an exponential decay. An exponential decay can imply that the postbrachytherapy death of each tumor cell is a stochastic Markovian process that is independent of the death of other tumor cells.

Adult↗

PubMed2002

p53 Immunoreactivity, Ki-67 expression, and microcirculation patterns in melanoma of the iris, ciliary body, and choroid.

PURPOSE: The major role of p53 is to modulate cell proliferation, but recently, it has been found that p53 also modulates angiogenesis through several pathways. Because both cellular proliferation and microcirculation patterns are important prognostic markers in uveal melanoma, we tested the relationships between p53 expression, the expression of the cell proliferation marker Ki-67, and the presence of various microcirculation patterns in uveal melanoma. METHODS: Immunostaining of p53 and Ki-67 using the bp53.12 and the MIB-1 antibodies, respectively, were preformed in 98 uveal melanomas (18 melanomas confined to the iris, 30 ciliary body melanomas, and 50 choroidal melanomas). Percent of p53 positive cells, and the mean MIB-1 positive cell count per high power field were calculated in each section by two observers. Microcirculation patterns were assessed in adjacent PAS stained sections. RESULTS: p53 immunoreactivity was found in 14 of the 98 melanomas. High proliferative activity and epithelioid cell type were associated with p53 immunoreactivity. However, p53 immunoreactivity was not associated with any of the microcirculation patterns or with tumor location. CONCLUSIONS: The findings suggest that alterations in p53 expression are associated with the expression of the cellular proliferation marker, Ki-67, but are not associated with the presence of microcirculation patterns.

Ciliary Body↗