Vessel Formation by Choroidal Endothelial Cells In Vitro Is Modulated by Retinal Pigment Epithelial Cells

The microcirculation of choroidal and ciliary body melanomas

“…In a preliminary matched-pair case-control study of 40 patients with choroidal or ciliary body melanoma, the presence of vascular loops was associated with death from metastatic melanoma,4 o a finding con- firmed recently by Sakamoto et al 42 In a larger series of 234 patients, Kaplan-Meier survival curves generated from deaths due to metastatic melanoma indicated that at lO-year follow-up the survival of patients whose tumour lacked the vascular patterns of parallel vessels with cross-linking, loops and networks was significantly better (91.7%, 91.1 % and 88.3%, respectively) than for patients whose tumours contained these patterns (56.9%, 55.4% and 50.7%; p = 0.0001 for all comparisons, n = 234). A Cox proportional hazards model was generated that permitted inclusion of the conventional prognostic factors (including the largest tumour dimension in contact with the sclera, cell type, tumour infiltrating lymphocytes, mitotic figures, gender, and location of the tumour within the eye) and the presence or absence of each of the nine microcirculatory pat terns.…”

Vascular endothelial growth factor in eye disease

“…In addition, vision loss can occur from atrophic AMD and geographic atrophy, and patients with neovascular AMD can have geographic atrophy in the same eye (Sunness et al, 1999). Thus, inhibiting VEGF (a survival factor for endothelial and neural cells (Blaauwgeers et al, 1999;Witmer et al, 2003;Saint-Geniez et al, 2006;Korte et al, 1984;Sakamoto et al, 1995;Hoffmann et al, 2000)) could conceivably lead to geographic atrophy and poor visual acuity in some patients with neovascular AMD. It is, therefore, important to titer the degree of VEGF blockade or specifically and selectively inhibit one or a few of the angiogenic actions of VEGF when considering VEGF inhibition as a treatment strategy.…”

“…18) and the role of VEGF as a survival factor. Relevant results include: 1) that RPE induced tube formation of CEC (Sakamoto et al, 1995); 2) that conditional inactivation of VEGF in RPE prevented choriocapillaris development (Marneros et al, 2005); 3) that loss of the choriocapillaris occurred after selective toxins to the RPE (Korte et al, 1984); and 4) that a chimeric toxin to VEGF 165 caused both RPE and CEC death (Hoffmann et al, 2000). In addition, the finding that VEGF receptors are expressed by retinal neurons suggests that it is also important to inner retinal neuronal health (Witmer et al, 2003;Kim et al, 1999).…”

“…There is, however, concern of the long-term effects on retinal cell survival after broad inhibition of VEGF activity (Blaauwgeers et al, 1999;Witmer et al, 2003;SaintGeniez et al, 2006;Korte et al, 1984;Sakamoto et al, 1995;Hoffmann et al, 2000). Finally, successful treatment of CNV through inhibition of VEGF may depend on the composition of the ECM, and anti-VEGF treatment may at times counter the goal to reduce CNV (Nozaki et al, 2006).…”

Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells

“…The inflammatory response in AMD lesions is characterized by an infiltration of the blood-retina barrier including RPE layer, by macrophages and lymphocytes (Seregard et al, 1994;Reddy et al, 1995;Penfold et al, 2001;Grossniklaus et al, 2002). In AMD, reactive, migrating or proliferating RPE cells are found adjacent to newly formed vessels in the subretinal space of wet AMD lesions (Miller et al, 1986;Sakamoto et al, 1995). Activation of RPE, inflammatory and endothelial cells may result in the release of a plethora of inflammatory mediators that individually or in concert may induce pathological changes in the retina.…”