Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Retinal Neovascularization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed2002

Angiotensin II stimulates migration of retinal microvascular pericytes: involvement of TGF-beta and PDGF-BB.

We studied the promigratory effect of angiotensin II (ANG II) on cultured bovine retinal microvascular pericytes. ANG II stimulated migration of pericytes by 86% at 10(-8) M, but this effect was lost at 10(-4) M. Migratory responses were inhibited by the ANG II type 1 (AT(1)) receptor antagonist losartan but not by PD-123319, an AT(2) antagonist. Addition of PD-123319 to the 10(-4) M ANG II dose restored migratory responses. The promigratory effect of ANG II (10(-7) M) was reduced by 59% in absence of gradient. Although ANG II augmented the latent matrix metalloproteinase-2 (MMP-2) activity of the pericyte by 35%, it also doubled tissue inhibitors of MMPs. ANG II-induced migration was not altered by a broad-spectrum MMP inhibitor (GM6001); it was inhibited by ~50% by antibodies against transforming growth factor (TGF)-beta(1/2/3) and was abolished by antibodies against platelet-derived growth factor (PDGF)-BB. We conclude that ANG II induces chemotactic responses on retinal microvascular pericytes acting through the AT(1) receptor. This effect is opposed by the AT(2) receptor. ANG II-induced chemotaxis is mediated by PDGF-BB and involves TGF-beta, but it is independent of MMP activity. It is also independent of vascular endothelial growth factor (VEGF) because VEGF did not stimulate pericyte migration. ANG II can contribute to the regulation of retinal neovascularization by stimulating pericyte migration.

Angiotensin II↗
PubMed1990

Effects of changes in oxygen tension on lipoxygenase metabolites. Serum 15-HETE is increased in kittens exposed to hyperoxia.

The chronic phase of O2-induced retinopathy is characterized by retinal neovascularization. We have previously demonstrated that 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE), a product of white cells, is proangiogenic. In this study, kittens exposed to in vivo hyperoxia produced increased amounts of 15-HETE. Nine litters of 30 kittens (aged 6-8 days) were used. Control kittens were left in room air; hyperoxic kittens were placed in 80% oxygen for 48 h; recovery kittens were returned to room air for 24 h following hyperoxic exposure. Following treatments, the animals were sacrified, and blood was evaluated for 15-HETE. Stimulated serum 15-HETE levels were assayed by high-performance liquid chromatography and GC-selected ion monitoring. While controls produced 0.48 +/- 0.16 (SE) nmol/ml of 15-HETE, values in the hyperoxic and recovery animals were increased at 0.7 +/0 0.2 and 0.68 +/- 0.15 nmol/ml (p less than 0.05 and p = 0.05, respectively). Increased production of this proangiogenic metabolite by WBCs (which can migrate out of blood vessels to set up extravascular angiogenic foci) may play a role in the genesis of the neovascularization process that occurs in response to oxygen-induced injury.

Animals↗
PubMed1989

Histopathology findings following retinal tack implantation.

For the first time this report describes the histopathological findings 2 months after retinal-tack implantation in a human eye. A stainless-steel tack was implanted to seal a small retinal tear during vitrectomy because of severe proliferative diabetic retinopathy in a 38-year-old man. By gross examination the enucleated eye showed a total retinal detachment except at the site where the tack had been implanted. Histologically a fibrovascular tissue proliferation arising from the choroid had grown into the adjacent retina at the tack site. No inflammatory reaction, pigment epithelium proliferation or glial-cell proliferation attributable to the tack were observed.

Adult↗
PubMed1992

Role of diabetes mellitus on the natural history of central retinal vein occlusion.

In order to elucidate the role of diabetes mellitus on the natural history of central retinal vein occlusion, we compared two groups of central retinal vein occlusion, one with diabetes mellitus (32 patients) and one without diabetes mellitus (113 patients). The two groups were quite similar with respect to age, sex, systemic hypertension and glaucoma. No fellow eye had proliferative diabetic retinopathy. The diabetic group had angiographically a more ischemic type of central retinal vein occlusion (72%) than the nondiabetic group (39%; p less than 0.002). Diabetics with central retinal vein occlusion should be closely monitored.

Adolescent↗
PubMed2003

COX-2 inhibition and retinal angiogenesis in a mouse model of retinopathy of prematurity.

PURPOSE: The prostaglandin-cyclooxygenase (COX) pathway influences new blood vessel growth in a variety of tissues. This study was conducted to determine the cellular location of COX-2 in the retina and whether the inhibition of COX-2 would reduce retinal angiogenesis in a rodent model of retinopathy of prematurity (ROP). METHODS: ROP was induced in C57BL/6 mice by exposing 7-day-old mice to 75% oxygen (hyperoxia) for 5 days followed by 5 days in room air (relative hypoxia and retinal angiogenesis). Normal mice were those with a normally developing retinal vasculature exposed to room air from birth until postnatal day (P)17. The COX-2 inhibitor, rofecoxib (15 mg/kg body weight intraperitoneally) was administered to normal and ROP mice from P12 to P17. Immunohistochemistry for COX-2 was performed on retinas from all groups by the avidin-biotin method. Histologic methods were used to count blood vessel profiles (BVPs) in the inner retina (inner limiting membrane, ganglion cell layer, and inner plexiform layer) with a masked approach. RESULTS: Intense COX-2 immunolabeling was specifically localized to ganglion cells and blood vessels of all mice retinas. In ROP mice, COX-2 immunolabeling was detected on blood vessels extending into the vitreous cavity. Quantitation of BVPs in the inner retina revealed an increase in untreated ROP mice compared with untreated normal mice (P < 0.001). Rofecoxib decreased BVPs by approximately 45% in normal mice and 37% in ROP mice. CONCLUSIONS: COX-2 is localized to sites associated with retinal blood vessels. The finding that the selective COX-2 inhibitor, rofecoxib, attenuated the retinal angiogenesis that accompanies ROP, and normal retinal development indicates that COX-2 plays an important role in blood vessel formation in the retina.

Animals↗
PubMed2003

Role of hypoxia during normal retinal vessel development and in experimental retinopathy of prematurity.

PURPOSE: To test the hypothesis that retinal hypoxia is present during vascular development in normal rat pups and in a newborn rat model of retinopathy of prematurity (ROP). METHODS: Preretinal vitreous PO(2) measurements were made during room air breathing using (19)F magnetic resonance spectroscopy (MRS) and a perfluoro-15-crown-5-ether droplet in normal adult and newborn (postnatal day [P]1-P20) rats, and in newborn rats exposed first to 14 days of variable oxygen (before NV) and six additional days in room air after variable oxygen exposure (during NV). After each experiment, blood gas values were measured, and retinas were isolated. Retinas were adenosine diphosphatase (ADPase) stained, and flatmounted to determine peripheral avascular extent and NV incidence and severity. RESULTS: In the vascularized rat retina, no significant difference (P > 0.05) was found between the droplet-derived preretinal vitreous oxygen tension (24 +/- 2 mm Hg, mean +/- SEM, n = 18) and previously reported electrode-measured oxygen tension (22 +/- 1 mm Hg). Only during normal retinal vessel growth (P1-P10) and before the appearance of NV was evidence for retinal hypoxia found at the border of the vascular and avascular retina. However, the mean PO(2) (range, 24-28 mm Hg) over the vascular retina was not different (P > 0.05) between any of the newborn rat groups in this study. CONCLUSIONS: (19)F MRS of a perfluorocarbon droplet provides an accurate measure of preretinal vitreous oxygen tension in rats. These data support an important role of physiologic hypoxia in normal retinal circulatory development and raises the possibility that, in experimental ROP, retinal hypoxia is a necessary but not sufficient condition for the development of retinal NV.

Animals↗
PubMed2004

Norrie gene product is necessary for regression of hyaloid vessels.

PURPOSE: To investigate the nature and origin of the vitreous membranes in mice with knock-out of the Norrie gene product (ND mice). METHODS: Eighty-two eyes of ND mice of different age groups (postnatal day [P]0-13 months) and 95 age-matched wild-type control mice were investigated. In vitreoretinal wholemounts and in sagittal sections, vessels and free cells were visualized by labeling for lectin. In addition, staining with a marker for macrophages (F4/80) and collagen XVIII/endostatin known to be involved in regression of hyaloid vessels was performed for light and electron microscopic investigations. Endostatin expression was confirmed by Western blot analysis. RESULTS: Wild-type controls showed the typical pattern of hyaloid vessels, their regression and concomitantly retinal vasculogenesis and angiogenesis. Hyaloid vessels all stained for endostatin, whereas retinal vessels remained unstained. In ND mice, 1 to 5 days after birth, the hyaloid and retinal vasculatures were comparable to that in control mice. The hyaloid vessels also stained for endostatin. Numerous F4/80-positive cells were present adjacent to the vessels. With increasing age, only a few connecting branches of the hyaloid vessels regressed. Even in old mice most of the hyaloid vessels persisted. The vessels still stained for endostatin. Retinal angiogenesis was impaired. CONCLUSIONS: Retrolental membranes in ND mice consist of persistent hyaloid vessels, indicating that the ND gene product is important for the process of regression of these vessels. The ND gene product neither influences endostatin expression nor the presence of macrophages.

Animals↗
PubMed2005

Strain-dependent differences in oxygen-induced retinopathy in the inbred rat.

PURPOSE: To examine the susceptibilities of different rat strains to oxygen-induced retinopathy, a model of human retinopathy of prematurity. METHODS: Litters of newborn rats of five inbred strains (Fischer 344 [F344], Dark Agouti [DA], Sprague-Dawley [SD], Wistar-Furth [WF], Lewis [LEW]) and one outbred strain (Hooded Wistar [HW]) were maintained in room air or were exposed to alternating 24-hour cycles of hyperoxia (80% oxygen in air) and normoxia (21% oxygen in air) for 14 days and were killed for analysis, either immediately (postnatal day 14, [P14]) or after 4 days in room air (P18). The fluorophore-conjugated isolectin GS-IB4 was used to label the endothelial cells of wholemounted retinas, and digital images were analyzed for avascular area and for morphologic abnormalities. RESULTS: Exposure to cyclic hyperoxia inhibited retinal vascularization in all strains relative to age-matched room air control animals. Total retinal avascular area at P14 after cyclic hyperoxia varied significantly among strains (P < 0.001). Avascular areas were smallest for the albino F344, WF, and LEW strains; larger for the albino SD strain; and largest for the pigmented DA and HW strains. Susceptibility to hyperoxic vascular attenuation was associated with ocular pigmentation, but neither with body mass nor with natural variation in litter size. Room air exposure for 4 days after cyclic hyperoxia was also associated with strain-related differences in retinal vascularization and with abnormalities in vascular morphology (P < 0.05). For all strains, the size of the avascular retinal area at P14 was predictive of the severity of morphologic abnormality at P18. CONCLUSIONS: Marked and consistent variations in the response of different inbred rat strains to cyclic hyperoxia were observed, suggestive of a genetic component to oxygen-induced retinopathy.

Animals↗
PubMed2005

Role of the Norrie disease pseudoglioma gene in sprouting angiogenesis during development of the retinal vasculature.

PURPOSE: To characterize developmental defects and the time course of Norrie disease in retinal and hyaloid vasculature during retinal development and to identify underlying molecular angiogenic pathways that may be affected in Norrie disease, exudative vitreoretinopathy, retinopathy of prematurity, and Coats' disease. METHODS: Norrie disease pseudoglioma homologue (Ndph)-knockout mice were studied during retinal development at early postnatal (p) stages (p5, p10, p15, and p21). Histologic techniques, quantitative RT-PCR, ELISA, and Western blot analyses provided molecular data, and scanning laser ophthalmoscopy (SLO) angiography and electroretinography (ERG) were used to obtain in vivo data. RESULTS: The data showed that regression of the hyaloid vasculature of Ndph-knockout mice occurred but was drastically delayed. The development of the superficial retinal vasculature was strongly delayed, whereas the deep retinal vasculature did not form because of the blockage of vessel outgrowth into the deep retinal layers. Subsequently, microaneurysm-like lesions formed. Several angiogenic factors were differentially transcribed during retinal development. Increased levels of hypoxia inducible factor-1alpha (HIF1alpha) and VEGFA, as well as a characteristic ERG pattern, confirmed hypoxic conditions in the inner retina of the Ndph-knockout mouse. CONCLUSIONS: These data provide evidence for a crucial role of Norrin in hyaloid vessel regression and in sprouting angiogenesis during retinal vascular development, especially in the development of the deep retinal capillary networks. They also suggest an early and a late phase of Norrie disease and may provide an explanation for similar phenotypic features of allelic retinal diseases in mice and patients as secondary consequences of pathologic hypoxia.

Animals↗
PubMed2006

Pharmacologic manipulation of sphingosine kinase in retinal endothelial cells: implications for angiogenic ocular diseases.

PURPOSE: The increased vascular permeability and pathogenic angiogenesis observed in diabetic retinopathy are induced, at least in part, by local inflammation and vascular endothelial growth factor (VEGF). Therefore, inhibition of signaling from VEGF and tumor necrosis factor-alpha (TNFalpha) is a promising approach to the treatment of this disease, as well as ocular diseases with similar etiologies, including age-related macular degeneration. A growing body of evidence demonstrates that sphingosine kinase (SK) plays an important role in cellular proliferation and angiogenesis. This study was undertaken to examine the effects of SK inhibitors on the responses of retinal endothelial cells (RECs) to VEGF and TNFalpha and their therapeutic efficacy in a diabetic retinopathy model. METHODS: The expression and function of SK in bovine and human RECs were examined by immunoblot analysis. The involvement of SK in mediating responses to VEGF and TNFalpha was examined by using pharmacologic inhibitors of SK in cellular and in vivo assays, including a 3-month streptozotocin-induced diabetic retinopathy model in rats. RESULTS: SK was present and active in human and bovine RECs, and SK activity in these cells was stimulated by VEGF. Inhibitors of SK blocked VEGF-induced production of sphingosine 1-phosphate and markedly attenuated VEGF-induced proliferation and migration of RECs. In addition, SK inhibitors were shown to block TNFalpha-induced expression of adhesion proteins, suppress VEGF-induced vascular leakage in an in vivo mouse model, and reduce retinal vascular leakage in the rat diabetic retinopathy model. CONCLUSIONS: Overall, these studies demonstrate that inhibitors of SK attenuate the effects of proliferative and inflammatory stimuli on RECs both in vitro and in vivo, and so could be significant therapeutics in the treatment of diabetic retinopathy.

Animals↗
PubMed2006

Comparative effects of early postnatal ibuprofen and indomethacin on VEGF, IGF-I, and GH during rat ocular development.

PURPOSE: Ibuprofen and indomethacin are nonselective prostaglandin synthetase inhibitors that have been shown to improve oxygen-induced retinopathy in mice. Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, and growth hormone (GH) are potent growth factors involved in retinal development. This study was conducted to examine and compare the effects of early postnatal ibuprofen and indomethacin on ocular and systemic VEGF, IGF-I, and GH during rat ocular development. METHODS: Newborn rats were treated with intraperitoneal injections of low and high doses of ibuprofen or indomethacin at birth (postnatal day [P]1) and on P2 and P3. A control group received equivalent volumes of saline. At P14, vitreous fluid, retinal homogenates, and serum were analyzed for VEGF, IGF-I, and GH protein levels. Retinal mRNA expression of VEGF splice variants (VEGF188, VEGF164, VEGF120), VEGF receptors (VEGFR-1, VEGFR-2, Npn-1, Npn-2), and pigment epithelium-derived factor (PEDF) were also examined. RESULTS: Animals treated with high-dose ibuprofen had significantly lower somatic growth and higher serum and vitreous IGF-I levels. High-dose ibuprofen decreased retinal VEGF levels and retinal VEGF164, VEGF120, and VEGFR-2 transcripts, resulting in a significant increase in the cecal period in 87% of rats at P14. Both indomethacin doses suppressed retinal VEGF164 transcripts without affecting VEGF receptors. CONCLUSIONS: Ibuprofen may be more effective than indomethacin for suppression of retinal VEGF signaling, suggesting a possible therapy for retinal neovascularization. However, deficits in somatic growth concurrent with higher systemic IGF-I levels suggests decreased IGF-I bioactivity. These adverse effects should be considered.

Animals↗
PubMed2003

Selective stimulation of VEGFR-1 prevents oxygen-induced retinal vascular degeneration in retinopathy of prematurity.

Oxygen administration to immature neonates suppresses VEGF-A expression in the retina, resulting in the catastrophic vessel loss that initiates retinopathy of prematurity. To investigate the mechanisms responsible for survival of blood vessels in the developing retina, we characterized two VEGF-A receptors, VEGF receptor-1 (VEGFR-1, also known as Flt-1) and VEGF receptor-2 (VEGFR-2, also known as Flk-1). Surprisingly, these two VEGF-A receptors differed markedly during normal retinal development in mice. At 5 days postpartum (P5), VEGFR-1 protein was colocalized with retinal vessels, whereas VEGFR-2 was detected only in the neural retina. Real-time RT-PCR identified a 60-fold induction of VEGFR-1 mRNA in retina from P3 (early vascularization) to P26 (fully vascularized), and no significant change in VEGFR-2 mRNA expression. Placental growth factor-1 (PlGF-1), which exclusively binds VEGFR-1, decreased hyperoxia-induced retinal vaso-obliteration from 22.2% to 5.1%, whereas VEGF-E, which exclusively binds VEGFR-2, had no effect on blood vessel survival. Importantly, under the same conditions, PlGF-1 did not increase vasoproliferation during (a). normal vessel growth, (b). revascularization following hyperoxia-induced ischemia, or (c). the vasoproliferative phase, indicating a selective function supporting blood vessel survival. We conclude that VEGFR-1 is critical in maintaining the vasculature of the neonatal retina, and that activation of VEGFR-1 by PlGF-1 is a selective strategy for preventing oxygen-induced retinal ischemia without provoking retinal neovascularization.

Animals↗
PubMedDate not supplied

The prognostic value of post-treatment retinopathy after panretinal photocoagulation for proliferative diabetic retinopathy in type 1 diabetes.

PURPOSE: To study the prognostic value of post-treatment retinopathy after panretinal laser photocoagulation for proliferative diabetic retinopathy in type 1 diabetes mellitus. Proliferative diabetic retinopathy is treated with panretinal photocoagulation, which significantly reduces the risk of visual loss from this complication. However, no parameters are presently known that can be used to define an optimal control interval after the initial panretinal photocoagulation treatment that ensures enhancement of the treatment in cases where this is needed. METHODS: In this retrospective cohort study, 85 eyes from 56 type 1 diabetic patients were identified who had been subjected to panretinal photocoagulation for proliferative diabetic retinopathy before 1990. The patients were divided into two groups: Group 1 had four or fewer microaneurysms only at the first post-treatment examination whereas Group 2 had more retinopathy. RESULTS: At the first photographic examination after treatment the eyes in Group 1 had a significantly lower visual acuity (VA) (mean =0.23, range: 0.01-1.00) than the patients in Group 2 (mean=0.48, range: 0.01-1.6). During the follow-up period the VA was further reduced in Group 2 but not in Group 1. Three eyes out of six in Group 1 had improvement of VA from below to above 0.1, whereas 6 eyes out of 12 in Group 2 experienced progression of retinopathy with a consequent worsening of VA to below 0.1 after a mean of 10.8 years (range: 6.8-15.9) after treatment. CONCLUSIONS: The severity of post-treatment retinopathy can be used to assess the need for enhancing photocoagulation of proliferative diabetic retinopathy in type 1 diabetes. The interval between post-treatment examinations can be increased to several years when the initial treatment has reduced retinopathy to a minimal level.

Adult↗
PubMed2001

CD13/APN is activated by angiogenic signals and is essential for capillary tube formation.

In the hematopoietic compartment, the CD13/APN metalloprotease is one of the earliest markers of cells committed to the myeloid lineage where it is expressed exclusively on the surface of myeloid progenitors and their differentiated progeny. CD13/APN is also found in nonhematopoietic tissues, and its novel expression on the endothelial cells of angiogenic, but not normal, vasculature was recently described. Treatment of animals with CD13/APN inhibitors significantly impaired retinal neovascularization, chorioallantoic membrane angiogenesis, and xenograft tumor growth, indicating that CD13/APN plays an important functional role in vasculogenesis and identifying it as a critical regulator of angiogenesis. To investigate the mechanisms of CD13/APN induction in tumor vasculature, the regulation of CD13/APN by factors contributing to angiogenic progression was studied. In this report, it is shown that endogenous CD13/APN levels in primary cells and cell lines are up-regulated in response to hypoxia, angiogenic growth factors, and signals regulating capillary tube formation during angiogenesis. Transcription of reporter plasmids containing CD13/APN proximal promoter sequences is significantly increased in response to the same angiogenic signals that regulate the expression of the endogenous gene and in human tumor xenografts, indicating that this fragment contains elements essential for the angiogenic induction of CD13/APN expression. Finally, functional antagonists of CD13/APN interfere with tube formation but not proliferation of primary vascular endothelial cells, suggesting that CD13/APN functions in the control of endothelial cell morphogenesis. These studies clearly establish the CD13/APN metalloprotease as an important regulator of endothelial morphogenesis during angiogenesis.

Angiogenesis Inducing Agents↗
PubMed1998

Increased serum concentrations of human hepatocyte growth factor in proliferative diabetic retinopathy.

Human hepatocyte growth factor (hHGF) is a powerful inducer of angiogenesis. We investigated the relationship between serum hHGF concentrations and proliferative diabetic retinopathy, the major characteristic of which is retinal neovascularization. Serum hHGF concentrations were measured in diabetic (n = 135) and nondiabetic subjects (n = 80). The mean serum hHGF concentration in diabetic subjects without retinopathy was lower than that in nondiabetic subjects [0.041 +/- 0.003 ng/mL (n = 62) vs. 0.080 +/- 0.010 ng/mL (n = 80); P < 0.05], but was not different from that in diabetic subjects with background retinopathy (0.058 +/- 0.007 ng/mL; n = 26) or preproliferative retinopathy (0.048 +/- 0.010 ng/mL; n = 10). The mean serum hHGF concentration was increased in subjects with proliferative retinopathy who had not undergone photocoagulation (0.213 +/- 0.025 ng/mL; n = 24), but not in those who had undergone photocoagulation (0.040 +/- 0.008 ng/mL; n = 13). Circulating hHGF may be involved in the mechanism of neovascularization in the proliferative diabetic retinopathy, and measurement of serum hHGF may be helpful in predicting the presence of proliferative retinopathy in diabetic subjects.

Adult↗
PubMed2005

Genistein inhibited hypoxia-inducible factor-1alpha expression induced by hypoxia and cobalt chloride in human retinal pigment epithelium cells.

The time-dependent changes of hypoxia-inducible factor-1alpha (HIF-1alpha) expression induced by hypoxia and CoCl2 treatment and the effects of genistein on the level of HIF-1alpha expression in human retinal pigment epithelium cells were examined. Judging by relative fluorescence using a confocal scanning laser microscope coupled to a computer, HIF-1alpha expression was determined. It was found that hypoxia could markedly increase the expression of HIF-1alpha. The highest expression of HIF-1alpha was detected at 1 h, which was 313.9% +/- 38.2% of the control level. After pretreatment with genistein (50, 100, and 200 micromol/l), the hypoxia-evoked HIF-1alpha expression was concentration-dependently inhibited. CoCl2 treatment could significantly elevate the level of HIF-1alpha expression. At 0.5 h after CoCl2 treatment, the highest level was observed, which was 141.4% +/- 14.1% of the control level. Genistein 50, 100, 200 micromol/L could also suppress HIF-1alpha expression in a concentration-dependent manner. These results suggested that the inhibition of HIF-1alpha protein expression by genistein may partly account for its effect on retinal neovascularization in vivo.

Cell Hypoxia↗
PubMed2003

Retinopathy of prematurity: molecular pathology and therapeutic strategies.

Retinopathy of prematurity (ROP) is an ischemia-induced proliferative retinopathy, which affects premature infants with low birth weight. It is a leading cause of visual impairment and blindness in children, and shares pathophysiological characteristics with other common ocular diseases such as diabetic retinopathy, central vein occlusion, and age-related macular degeneration. Pathologically similar inherited diseases such as Norrie disease suggest a possible genetic component in the susceptibility to ROP. The process of retinal neovascularization in ROP and in animal models of oxygen-induced retinopathy is complex, and involves angiogenic factors, such as vascular endothelial growth factor, and basement membrane components. Potential medical therapies for ROP, including modulators of angiogenic factors, inhibitors of basement membrane changes, endogenous inhibitors such as pigment epithelium derived factor, and anti-inflammatory drugs, have shown efficacy against neovascularization in several animal models. Some of these therapies are in clinical trials now for diabetic retinopathy and age-related macular degeneration, and in the future may prove efficacious for the treatment of ROP.

Angiogenesis Inducing Agents↗
PubMed2003

Pharmacokinetics of topical ocular drug delivery: potential uses for the treatment of diseases of the posterior segment and beyond.

In developing a drug delivery strategy, issues of absorption, distribution, metabolism, and elimination must be considered. The eye presents unique opportunities and challenges when it comes to the delivery of pharmaceuticals, and is most accessible to the application of topical medications. While absorption by this route is inefficient, there are few side effects. While it has been assumed that topically applied drugs penetrated into the intraocular environment through the cornea, this is currently being reassessed. More recent investigations have shown that the conjunctival route of entry plays an important role in the penetration of drugs into the anterior segment. Furthermore, topically applied drugs have been shown to have access to the sclera from the conjunctiva. As such, it is conceivable that such drugs could find their way to the posterior segment. Data suggest that the sclera is readily permeable to even large molecular weight compounds ( approximately 150 kD). The recent finding that topically applied nepafenac inhibited choroidal and retinal neovascularization by decreasing the production of VEGF, as well as our data showing that even a large molecular weight peptide like insulin can accumulate in the retina and optic nerve after topical application, supports the contention that topically applied drugs can not only reach the posterior segment, but that they can also be therapeutic. Finally, the implications of our findings that topically applied insulin also accumulates in the contralateral eye as well as in the central nervous system are discussed.

Absorption↗