Rohini M. Nair

Corneal Changes in Xeroderma Pigmentosum: A Clinicopathologic Report

PURPOSE To report the clinicopathologic features of corneal involvement in patients with xeroderma pigmentosum. DESIGN Retrospective review of corneal histopathology. METHODS Thirteen corneal specimens of 11 patients with xeroderma pigmentosum who underwent keratoplasty (lamellar/full-thickness) for corneal involvement were studied. Five-micrometer-thick sections were made from all the samples and stained using hematoxylin-eosin and periodic acid-Schiff stains. A light microscopic examination was performed to study the histopathologic changes. RESULTS The corneal findings on clinical examination were haze, scarring, vascularization, stromal edema, pigment clumps on endothelial surface, and corneal thinning. The histopathologic evaluation revealed changes in all layers of cornea. Epithelial changes seen were intraepithelial edema, fibrosis, epithelial downgrowths, and pannus formation. The Bowman membrane was fragmented or absent. Stroma was characterized by alteration in the lamellar pattern, scarring, edema, loss of keratocytic nuclei, and calcification. The Descemet membrane was thickened to a variable extent in most specimens and there was marked loss of endothelial cells in all. CONCLUSION Most histologic features are consistent with the previous few reports. The remarkable finding in all corneal specimens was a moderate to severe degree of loss of the endothelial cells. This noteworthy finding supports the ultraviolet (UV) radiation-induced endothelial cell damage in these patients. This has an important clinical implication when planning for anterior lamellar keratoplasty, as endothelial cell density may be subnormal in these patients.

Transgenic Models in Retinoblastoma Research

Understanding the mechanism of retinoblastoma (Rb) tumor initiation, development, progression and metastasis in vivo mandates the use of animal models that mimic this intraocular tumor in its genetic, anatomic, histologic and ultrastructural features. An early setback for developing mouse Rb models was that Rb mutations did not cause tumorigenesis in murine retinas. Subsequently, the discovery that the p107 protein takes over the role of pRb in mice led to the development of several animal models that phenotypically and histologically resemble the human form. This paper summarizes the transgenic models that have been developed over the last three decades.

Animal models in retinoblastoma research

Advances in animal models of retinoblastoma have accelerated research in this field, aiding in understanding tumor progression and assessing therapeutic modalities. The distinct pattern of mutations and specific location of this unique intraocular tumor have paved the way for two types of models- those based on genetic mutations, and xenograft models. Retinoblastoma gene knockouts with an additional loss of p107, p130, p53 and using promoters of Nestin, Chx10, and Pax6 genes show histological phenotypic changes close to the human form of retinoblastoma. Conditional knockout in specific layers of the developing retina has thrown light on the origin of this tumor. The use of xenograft models has overcome the obstacle of time delay in the presentation of symptoms, which remains a crucial drawback of genetic models. With the advances in molecular and imaging technologies, the current research aims to develop models that mimic all the features of retinoblastoma inclusive of its initiation, progression and metastasis. The combination of genetic and xenograft models in retinoblastoma research has and will help to pave way for better understanding of retinoblastoma tumor biology and also in designing and testing effective diagnostic and treatment modalities.

Animal Models of Ocular Tumors

Ocular oncology includes many rare malignancies, for which clinical trials are often logistically very difficult to undertake. Consequently, in order to test new drugs for ocular tumors, cell lines are often resorted to, and in vivo testing is often only possible in animal models. Many different animal models exist for ocular neoplasms, and these comprise mice, rats, chick embryos, zebrafish, and Drosophila animal models. They may also entail genetic modifications, as often seen in retinoblastoma studies, or use human cell lines or patient-derived xenografts (PDXs). Herein, the most important animal models for conjunctival and uveal melanoma, vitreoretinal lymphoma, and retinoblastoma are discussed, based on recent reviews in “Ocular Oncology and Pathology.”