OBJECTIVESThe aim of this study was to evaluate heat shock protein 90 (HSP90) expression in squamous lesions (SLs) and to assess its diagnostic value for different lesions within the SL spectrum.METHODSA total of 70 conjunctival SLs, including 19 papillomas, 22 cases of conjunctival intraepithelial neoplasia (ConINs) I, 11 cases of ConIN II, six cases of ConIN III, and 12 squamous carcinomas (sqCAs), were evaluated using the German immunoreactive score against HSP90.RESULTSCytoplasmic HSP90 expression differed between low- and high-grade lesions (P < .001). Among high-grade lesions, the nuclear HSP90 score was higher in the ConIN III-sqCA group than in the ConIN II group (P = .0162). A percentage of total thickness staining of less than 73% differentiated between ConIN III and sqCA.CONCLUSIONSThe expression of HSP90 is particularly useful to differentiate low-grade from high-grade lesions of the conjunctiva. HSP90 may play an important role in the malignant transformation of SLs and could be a new target for therapy.
Bilateral Fuchs uveitis associated with vitreous infiltration and posterior segment involvement requires a thorough diagnostic evaluation. The lack of well-defined diagnostic criteria makes identification of this entity difficult. The aim of this case report was to present the characteristics of a patient with atypical Fuchs uveitis and the procedures needed to rule out the differential diagnosis with specific attention to the utility of in vivo confocal microscopy (IVCM). Case Report: One case of chronic bilateral uveitis with severe vitreous opacities is presented. After extensive systemic workup, including vitrectomy, the case had no identifiable systemic etiology. IVCM of the cornea revealed the presence of dendritiform keratic precipitates. Conclusion: The diagnosis of Fuchs uveitis is based on clinical findings as no confirmatory laboratory tests are available. A high index of suspicion is key to an early diagnosis, especially in the cases with vitreous opacities and posterior segment manifestations. Auxiliary tests such as IVCM may aid the clinician in the diagnosis of Fuchs uveitis.
INTRODUCTION:Focal adhesion kinase (FAK) is implicated in tumor progression and metastatic cascade, and has been shown to be overexpressed in a variety of human cancers. However, the role of FAK in human uveal melanoma (UM) is not well defined. The purpose of this study was to evaluate the expression of FAK in UM tumors and normal eyes, and to determine the effect of Hsp90 inhibition on FAK expression in UM cells. METHODS:FAK expression was assessed in 39 UM specimens, FAK[pY397] expression was assessed in 51 UM specimens, and both FAK and FAK[pY397] expression were assessed in 20 normal eyes. The expression of FAK and FAK[pY397] was detected by Western blot in five UM cell lines after treatment with 10 μmol/L of 17-AAG. RESULTS:FAK was positive in 87.2% and FAK[pY397] in 90% of UM specimens. Low FAK expression was detected in non-tumor structures and in normal eyes. The cell lines with the most proliferative, invasive phenotype (92.1, SP6.5 and MKT-BR) displayed high expression of FAK[pY397], and the levels of FAK and FAK[pY397] were decreased in the presence of 17-AAG starting with 24 h of exposure. CONCLUSION:FAK and FAK[pY397] were overexpressed in human UM tumors compared to normal ocular tissue and high levels of FAK[pY397] were seen in the most aggressive UM cell lines. Hsp90 inhibition led to downregulation of FAK expression. We propose a role for FAK in the pathogenesis of UM. Future studies are needed to explore the use of Hsp90 inhibitors as a feasible approach for modulating FAK in UM.
Introducao: As cinases de adesao focal (CAF) sao tirosina-cinases citoplasmaticas, nao receto- ras, importantes e no processo oncogenico. O objetivo deste estudo e avaliar o nivel de expressao das CAF no retinoblastoma e correlaciona-la com fatores prognosticos histopatologicos. Material e Metodos: a expressao de CAF e da sua forma ativa fosforilada - CAF [pY397] - foi avaliada em vinte especimes de retinoblastomas por imuno-histoquimica. A imunorreatividade foi correlacionada com a idade, grau de diferenciacao do tumor e com a presenca ou ausencia de invasao da camara anterior, coroideia, vitreo e nervo otico. Resultados: A avaliacao histopatologica revelou 55% de tumores pouco diferenciados, 30% moderadamente diferenciados e 15% bem diferenciados. A invasao da camara anterior foi obser- vada em 80% dos casos, da coroide em 35%, do vitreo em 25% e do nervo otico em 70%. Vinte e cinco por cento dos tumores apresentaram uma forte expressao de CAF [pY397], 60% expressao moderada e 15% expressao fraca. Relativamente a imunorreatividade para CAF nao fosforilada, 20% dos tumores revelaram-se fortemente positivos, 75% moderadamente positivos e 5% fraca- mente positivos. Nao houve correlacao significativa entre a expressao destas moleculas e a idade ou fatores de prognostico histopatologicos. Conclusao: Este estudo foi o primeiro a avaliar a expressao desta molecula no retinoblastoma. Todos os especimes apresentaram expressao de CAF ou CAF [pY397], tendo mais de 80% exi- bido expressao moderada ou forte de ambas. Os resultados sugerem uma potencial relacao destas moleculas com o processo oncogenico, abrindo perspetivas relativamente a novas estrategias de intervencao terapeutica no retinoblastoma.
Purpose: Recent studies have found that dysregulation of Toll-like receptor 3 (TLR3)-a key player in innate immunity-in retinal pigmented epithelium (RPE) may play a role in retinal oxidative stress. The aim of this study was to evaluate the expression of TLR3 in all layers of the normal human retina. Methods: Formalin-fixed, paraffin-embedded sections of human donor eyes-with no fundoscopic or microscopic evidence of disease-were used in this study. Mean age of donors was 62.8 ± 31.5 years (12 female, 7 male). Immunohistochemistry was performed using an antibody to human TLR3 and staining was scored according to intensity (0=negative, 1=low-to-moderate, 2=strong) and extent (0=negative, 1=staining ≤50% of cells, 2=staining >50% of cells) of staining. We compared the IRS between the layers in macular and peripheral retina. Results: TLR3 was found to be expressed in all layers of the retina, with differences seen within layers and between cases. The following layers were graded as having a strong IRS: Ganglion Cell, Outer Plexiform, Photoreceptors and RPE. The remaining layers were all graded as weak staining. No significant differences were seen between macular and peripheral retina for TLR3 staining in any retinal layer. Conclusion: Our results demonstrate that TLR3 can be found in all retinal layers. This study provides an overview of TLR3 expression throughout the human retina and thus can serve as a foundation for further research that evaluates aberrant TLR3 function or expression in an array of ophthalmic conditions, including those in which oxidative stress is a factor.
Objective: To assess the efficacy of transconjunctival trabeculectomy flap suturing (TTFS) in improving choroidal effusions and bleb dysesthesia resulting from overfiltration after trabeculectomy.Design: Retrospective review.Participants: The study involved 15 eyes 01 15 patients.Methods: Patients underwent TTFS for choroidal effusions and bleb dysesthesia following trabeculectomy using mitomycin C. The scleral flap was sutured through the conjunctiva as an outpatient clinic procedure.Results: There were 11 patients who had choroidal effusions and 4 patients were identified with dysesthesia. The average duration of choroidal effusion prior to TTFS was 2.1 +/- 2.3 months and 3 +/- 2 months in the dysesthesia group. At the final follow-up (25 +/- 17 months) the mean intraocular pressure improved from 4.1 +/- 2.1 mm Hg before suturing to 8.1 +/- 3.6 mm Hg (p < 0.007) for the patients with choroidal effusion and from 4.2 +/- 0.6 mm Hg to 8.7 +/- 3.5 mm Hg (p = 0.05) for the patients with dysesthesia. In both groups, resolution of the signs and symptoms was achieved in all cases. The mean time to resolution of choroidal effusions was 5.5 +/- 8.6 weeks and the mean time to resolution of dysesthesia was 2 +/- 0.8 weeks. None of the patients had serious complications such as failure of the trabeculectomy or visual loss.Conclusions: Transconjunctival suturing of the trabeculectomy scleral flap is a simple and effective surgical method for the treatment of cases of choroidal effusions or dysesthesia resulting from trabeculectomy.