[Retinal tumors in adults - Part 1: vascular tumors of the retina]. / Retinale Tumoren im Erwachsenenalter ­ Teil 1: Vaskuläre Tumoren der Retina.

Retinal tumors are a heterogeneous group of congenital and acquired lesions. In this review series the important retinal tumors are discussed and presented in two articles. In the first part of the article the most important vascular tumors of the retina are presented. Even with benign tumors visual symptoms, such as exudative retinal detachment occur, which often lead to irreversible visual impairments. Because visual symptoms are often a manifestation of systemic diseases, the ophthalmologist plays an important role in the accurate and early diagnosis of retinal tumors. This article reviews the most important clinical and diagnostic features of retinal vascular tumors in adults, their systemic associations and the literature on currently available treatment strategies.

[Retinal tumors in adults: Part 2 nonvascular tumors of retina and retinal pigment epithelium]. / Retinale Tumoren im Erwachsenenalter ­ Teil 2: Nichtvaskuläre Tumoren der Retina und des retinalen Pigmentepithels.

Retinal tumors are a heterogeneous group of congenital and acquired lesions. In the second part of the article retinocytic and glial cell tumors of the retina, tumors of the retinal pigment epithelium, malignant tumors, such as lymphomas and metastases are presented. In benign and malignant tumors visual symptoms, such as exudative retinal detachment occur, which often lead to irreversible visual impairments. Because visual symptoms are often a manifestation of systemic diseases, the ophthalmologist plays an important role in the accurate and early diagnosis of retinal tumors. This article reviews the most important clinical and diagnostic features of retinal tumors in adults, the systemic associations and the literature on currently available treatment strategies.

Monosomy-3 Alters the Expression Profile of the Glucose Transporters GLUT1-3 in Uveal Melanoma.

Monosomy-3 in uveal melanoma (UM) cells increases the risk of fatal metastases. The gene encoding the low-affinity glucose transporter GLUT2 resides on chromosome 3q26.2. Here, we analyzed the expression of the glucose transporters GLUT1, GLUT2, and GLUT3 with regard to the histological and clinical factors by performing immunohistochemistry on the primary tumors of n = 33 UM patients. UMs with monosomy-3 exhibited a 57% lower immunoreactivity for GLUT2 and a 1.8×-fold higher ratio of GLUT1 to total GLUT1-3. The combined levels of GLUT1-3 proteins were reduced in the irradiated but not the non-irradiated tumors with monosomy-3. GLUT3 expression was stronger in the irradiated samples with disomy-3 versus monosomy-3, but the ratio of the GLUT3 isoform to total GLUT1-3 did not differ with regard to the monosomy-3 status in the irradiated or non-irradiated subgroups. Systemic metastases were associated with the presence of monosomy-3 in the primary and circulating tumor cells as well as a higher GLUT1 ratio. Upregulation of the high-affinity glucose transporter GLUT1 possibly as a compensation for the low-affinity isoform GLUT2 may be enhancing the basal glucose uptake in the UM cells with monosomy-3. Prevention of hyperglycemia might, therefore, be a valuable approach to delay the lethal UM metastases.

Metastasis of Uveal Melanoma with Monosomy-3 Is Associated with a Less Glycogenetic Gene Expression Profile and the Dysregulation of Glycogen Storage.

The prolonged storage of glucose as glycogen can promote the quiescence of tumor cells, whereas the accumulation of an aberrant form of glycogen without the primer protein glycogenin can induce the metabolic switch towards a glycolytic phenotype. Here, we analyzed the expression of n = 67 genes involved in glycogen metabolism on the uveal melanoma (UM) cohort of the Cancer Genome Atlas (TCGA) study and validated the differentially expressed genes in an independent cohort. We also evaluated the glycogen levels with regard to the prognostic factors via a differential periodic acid-Schiff (PAS) staining. UMs with monosomy-3 exhibited a less glycogenetic and more insulin-resistant gene expression profile, together with the reduction of glycogen levels, which were associated with the metastases. Expression of glycogenin-1 (Locus: 3q24) was lower in the monosomy-3 tumors, whereas the complementary isoform glycogenin-2 (Locus: Xp22.33) was upregulated in females. Remarkably, glycogen was more abundant in the monosomy-3 tumors of male versus female patients. We therefore provide the first evidence to the dysregulation of glycogen metabolism as a novel factor that may be aggravating the course of UM particularly in males.

Lower Levels of Adiponectin and Its Receptor Adipor1 in the Uveal Melanomas With Monosomy-3.

Purpose: Adiponectin is an insulin-sensitizing and anticarcinogenic hormone that is encoded by a gene on chromosome 3. Here, we analyzed the expression of adiponectin and its receptor Adipor1 in primary uveal melanoma (UM) with regard to the monosomy-3 status and clinical factors, as well as the physiological response of UM cells to adiponectin. Methods: Immunohistochemistry was performed on the primary UM of 34 patients. Circulating melanoma cells (CMC) were isolated by immunomagnetic enrichment. Monosomy-3 was evaluated by Immuno-FISH. Gene expression was analyzed using the RNAseq data of The Cancer Genome Atlas study. Cultures of choroidal melanocytes and UM were established from the samples of two patients. The proliferative potential of the UM cell lines Mel-270 and OMM-2.5 was determined by immunocytochemistry, immunoblotting, cell cycle analysis, nucleolar staining, and adenosine triphosphate (ATP) levels. Results: UM with monosomy-3 exhibited a lower immunoreactivity for adiponectin and Adipor1, which was associated with monosomy-3-positive CMC and the development of extraocular growth or metastases. Both proteins were more abundant in the irradiated tumors and present in the cultured cells. Gene expression profile indicated the impairment of adiponectin-mediated signaling in the monosomy-3 tumors. Adiponectin induced a significant decline in the ATP levels, Ki-67 expression, cells in the G2/M phase, and nucleolar integrity in UM cultures. Conclusions: Adiponectin deficiency appears to enhance the metastatic potential of the UM cells with monosomy-3 and the termination of tumor dormancy. Counteracting insulin resistance and improving the serum adiponectin levels might therefore be a valuable approach to prevent or delay the UM metastases.

[Alternative treatment options for periorbital basal cell carcinoma]. / Alternative Behandlungsoptionen beim Basalzellkarzinom am Auge.

BACKGROUND: Latest developments as well as established procedures offer alternative treatment approaches to basal cell carcinoma (BCC) when micrographically controlled surgical removal is not a valid option. OBJECTIVE: Alternative treatment options for periorbital BCC are presented. METHODS: A literature search was carried out and a structured display and analysis of the results are given. RESULTS: Micrographically controlled surgical removal represents the gold standard in treatment of BCC. When for various reasons surgical removal is not a valid option, other procedures are required. The alternative treatment options can be divided into three main groups: treatment options for locally advanced or metastasized BCC, topical approaches for small and superficial BCC and prophylactic measures. While radiotherapy and systemic therapy are suitable for locally advanced BCC and are discussed in a tumor board, small and superficial BCC can be treated by topical medication. In cases of a previous BCC history, a prophylactic treatment can be considered. Combinations of systemic treatment and also neoadjuvant or adjuvant approaches before and after surgery are promising options for a successful outcome, which can further improve the standard treatment for locally advanced BCC. CONCLUSION: Alternative treatment options for periocular BCC are available; however, the use is only indicated when microscopically controlled excision with subsequent oculoplastic reconstruction is not possible. According to the national guidelines a prior presentation to a suitable tumor board is practically compulsory.

Gene expression regulation in retinal pigment epithelial cells induced by viral RNA and viral/bacterial DNA.

PURPOSE: The pathogenesis of age-related macular degeneration (AMD) is associated with systemic and local inflammation. Various studies suggested that viral or bacterial infection may aggravate retinal inflammation in the aged retina. We compared the effects of synthetic viral RNA (poly(I:C)) and viral/bacterial DNA (CpG-ODN) on the expression of genes known to be involved in the development of AMD in retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were stimulated with poly(I:C; 500 µg/ml) or CpG-ODN (500 nM). Alterations in gene expression and protein secretion were determined with real-time RT-PCR and ELISA, respectively. Phosphorylation of signal transduction molecules was revealed by western blotting. RESULTS: Poly(I:C) induced gene expression of the pattern recognition receptor TLR3, transcription factors (HIF-1α, p65/NF-κB), the angiogenic factor bFGF, inflammatory factors (IL-1ß, IL-6, TNFα, MCP-1, MIP-2), and complement factors (C5, C9, CFB). Poly(I:C) also induced phosphorylation of ERK1/2 and p38 MAPK proteins, and the secretion of bFGF and TNFα from the cells. CpG-ODN induced moderate gene expression of transcription factors (p65/NF-κB, NFAT5) and complement factors (C5, C9), while it had no effect on the expression of various TLR, angiogenic factor, and inflammatory factor genes. The activities of various signal transduction pathways and transcription factors were differentially involved in mediating the poly(I:C)-induced transcriptional activation of distinct genes. CONCLUSIONS: The widespread effects of viral RNA, and the restricted effects of viral/bacterial DNA, on the gene expression pattern of RPE cells may suggest that viral RNA rather than viral/bacterial DNA induces physiologic alterations of RPE cells, which may aggravate inflammation in the aged retina. The data also suggest that selective inhibition of distinct signal transduction pathways or individual transcription factors may not be effective to inhibit viral retinal inflammation.