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At least 541 records · Page 30Linked to original sources
PubMed2006

Involvement of MAPKs in endostatin-mediated regulation of blood-retinal barrier function.

PURPOSE: This study aimed to evaluate the effects of endostatin on tight junction (TJ) integrity in retinal microvascular endothelial cells (RMECs) in vitro and in vivo. Moreover, it was hypothesized that endostatin-induced occludin upregulation regulated VEGF165-mediated increases in endothelial cell permeability and involved activation of the MAPK signaling cascade. Endostatin is a 20-kDa fragment of collagen XVIII that has been shown to be efficacious in the eye by preventing retinal neovascularization. Endostatin is a specific inhibitor of endothelial cell proliferation, migration, and angiogenesis and has been reported to reverse VEGF-mediated increases in vasopermeability and to promote integrity of the blood-retinal barrier (BRB). In order to determine the mechanism of endostatin action on BRB integrity, we have examined the effects of endostatin on a number of intracellular pathways implicated in endothelial cell physiology. METHODS: C57/Bl6 mice were injected with VEGF165 and/or endostatin, and the distribution of occludin staining was determined using retinal flatmounts. Western blot analysis of RMECs treated with VEGF165 and/or endostatin was used to determine changes in occludin expression and p38 MAPK and extracellular regulated kinase (ERK1/ERK2 MAPK) activation, while FD-4 flux across the RMEC monolayer was used to determine changes in paracellular permeability. RESULTS: Endostatin prevented the discontinuous pattern of occludin staining observed at the retinal blood vessels of mice administered an intraocular injection of VEGF165. It was shown that endostatin activated p38 MAPK 5 min after addition to RMECs and continued to do so for approximately 30 min. Endostatin was also shown to activate ERK1/ERK2 5 min after addition and continued to do so, albeit with less potency, up to and including 15 min after addition. Inhibition of p38 MAPK and ERK1/ERK2 prevented endostatin's ability to upregulate levels of occludin expression. Inhibition of these key signaling molecules was shown to prevent endostatin's ability to protect against VEGF165-mediated increases in paracellular permeability in vitro. However, it appears that p38 MAPK may play a more important role in VEGF-mediated permeability, as inhibition of ERK1/ERK2 will not prevent VEGF165-mediated permeability compared with control (untreated) cells or cells treated with both a p38 MAPK inhibitor and VEGF165. CONCLUSIONS: Occludin is important for the maintenance of tight junction integrity in vivo. In a p38 MAPK and ERK1/ERK2 dependent manner, endostatin was shown to upregulate the levels of expression of the tight junction protein occludin. Inhibition of these key MAPK components may prevent endostatin's ability to decrease VEGF165-induced paracellular permeability.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Ocular ischemic syndrome in diabetic patients.

PURPOSE: Diabetes mellitus aggravates carotid occlusive disease, that can manifest as ocular ischemic syndrome (OIS). Ocular manifestations and visual prognosis of OIS in diabetic patients were retrospectively analyzed. METHODS: Twenty-three consecutive diabetic patients with OIS were divided into two groups according to the presence of iris neovascularization, and the clinical features were reviewed. RESULTS: In the first group, 14 eyes of 12 diabetic patients (11 men and 1 woman) had no iris neovascularization. Two patients had bilateral OIS. The ages in this group ranged from 50-75 years. Four eyes with optic atrophy or ischemic optic neuropathy had severe visual loss. Six eyes with hypoperfusion retinopathy or retinal vein obstruction and 2 eyes with cataract had mild visual loss. Each eye with amaurosis fugax or retinal neovascularization had no visual deterioration. Asymmetrical retinopathy was observed in 2 patients. Carotid surgery stabilized and resolved amaurosis fugax and hypoperfusion retinopathy. In the second group, 11 eyes of 11 patients had iris neovascularization. The patients were all male and their ages ranged from 53-77 years. All eyes with iris neovascularization had severe visual deterioration. In 5 patients, asymmetrical ocular manifestation was observed. Carotid reconstruction surgery and ophthalmological treatment were not successful for recovering a satisfactory visual outcome in OIS. CONCLUSION: The features of OIS in diabetic patients mimic diabetic retinopathy and manifest with asymmetrical ocular findings. Iris neovascularization is an indicator of poor visual prognosis. It is essential to recognize the early stages of OIS associated with diabetes mellitus.

Aged↗
PubMed1995

Bilateral bullous exudative retinal detachment complicating idiopathic central serous chorioretinopathy during systemic corticosteroid therapy.

PURPOSE: To present evidence that systemic corticosteroid therapy may cause bilateral bullous serofibrinous exudative retinal detachment in some patients with idiopathic central serous chorioretinopathy. BACKGROUND: Idiopathic central serous chorioretinopathy usually causes mild, transient loss of central vision, usually in otherwise healthy men with a type A personality. A few patients have permanent visual loss because of chronic and recurrent retinal detachment. The clinical findings in these patients may lead to incorrect diagnoses and use of corticosteroid therapy. METHODS: The clinical and photographic records of three patients in whom bilateral bullous serofibrinous exudative retinal detachment associated with idiopathic central serous chorioretinopathy developed after treatment with systemic corticosteroids were reviewed. RESULTS: Systemic corticosteroid treatment was instituted (1) as a prophylaxis to prevent exacerbation of the disease while undergoing surgery in the fellow eye, and (2) as the result of misdiagnoses of multifocal choroiditis and retinal vasculitis (Eales disease). Two of the patients had a history of chronic recurrent retinal detachments before institution of corticosteroid treatment. In one of these patients, bilateral chronic inferior retinal detachment developed, causing peripheral retinal vascular nonperfusion, retinal neovascularization, and vitreous hemorrhage. All three patients had severe permanent visual loss in one or both eyes. CONCLUSION: The findings in these patients provide further evidence that systemic corticosteroid treatment may cause severe exacerbation of retinal detachment and lasting visual loss in some patients with idiopathic central serous retinopathy. Recognition of the atypical presentations of this disorder is important to avoid incorrect diagnoses and treatment.

Adrenal Cortex Hormones↗
PubMed1992

Current uses of ophthalmic lasers.

Current laser treatments are quick, relatively painless, and well tolerated. Some ophthalmic techniques can be performed only by laser while others have a lower morbidity than alternative treatments. Peripheral retinal photocoagulation and focal photocoagulation now offer greatly improved visual prognosis for diabetic patients with proliferative diabetic retinopathy or diabetic macular disease. Selected cases of macular degeneration may be treated by focal laser photocoagulation. The role of lasers in treating sub-retinal neovascular membranes is limited by the extent and location of the membrane at presentation and the high risk of recurrence after treatment. Patients with distorted vision must be referred urgently for specialist ophthalmic assessment. Flat retinal holes and tears may be sealed by laser therapy, thus preventing retinal detachment. Short pulsed neodymium-YAG photodisruptive capsulotomy effectively clears the visual axis of thickened posterior lens capsule after cataract surgery. Short pulsed neodymium-YAG photodisruptive iridotomy may be used to treat and prevent angle closure glaucoma. Laser trabeculoplasty aids the control of open angle glaucoma. Research is continuing into the role of other lasers in managing open angle glaucoma and of photoablative lasers in treating refractive errors and superficial corneal disorders.

Cataract Extraction↗
PubMed2001

Inducible nitric oxide synthase mediates the change from retinal to vitreal neovascularization in ischemic retinopathy.

Intravitreal neovascular diseases are a major cause of blindness worldwide. It remains unclear why neovessels in many retinal diseases spread into the physiologically nonvascularized vitreous rather than into the ischemic retinal areas, where the angiogenic factors are released. Here we show that inducible nitric oxide synthase (iNOS) is expressed in the ischemic retina. Using iNOS knockout mice and the iNOS inhibitor 1400W, we demonstrate that iNOS expression inhibits angiogenesis locally in the avascular retina, mediated at least in part by a downregulation of VEGF receptor 2 (VEGFR2) in cells adjacent to iNOS-expressing cells. At the same time, pathological intravitreal neovascularization is considerably stronger in iNOS-expressing animals. These findings demonstrate that iNOS plays a crucial role in retinal neovascular disease and show that it offers an ideal target for the control of vitreal neovascularization through improvement of the vascularization of the hypoxic retina.

Animals↗
PubMed1997

Vascular endothelial growth factor (VEGF) in normal human corneal epithelium: detection and physiological importance.

PURPOSE: Corneal neovascularization is a major challenge following chemical burns and corneal inflammation. The factors triggering corneal neovascularization involve various growth factors. In the release and control of these factors the regenerating tissue plays a decisive role. Only recently has vascular endothelial growth factor been shown to be involved in the basic events of retinal neovascularization. From the cornea current knowledge allows only for the statement that corneal epithelium could be able to produce vascular endothelial growth factor. The present study was designed to show the presence of vascular endothelial growth factor-like substances in the corneal epithelium of the normal eye in vivo. METHODS: Using specific antibodies to the N-terminus of human vascular endothelial growth factor indirect immuno-histochemistry was applied to sections of normal human corneal epithelium and to five sections of enucleated human eyes with a morphologically normal anterior segment. RESULTS: In all sections specific staining for vascular endothelial growth factor was found over the entire epithelium. Staining was most intense in the basal layer of epithelial cells. Only a weak staining was detectable in the cell layers closer to the surface. Here, however, the samples of corneal epithelium having been subject to traumatic erosion showed a slightly more intense staining than the sections from the undisturbed corneal tissue of whole globe sections. CONCLUSION: It was shown that vascular endothelial growth factor-like protein is present in the human corneal epithelium. Observed differences in the staining pattern could suggest that the expression of vascular endothelial growth factor might be enhanced due to ocular surface trauma. It is suggested that corneal epithel vascular endothelial growth factor might be an important factor in the cascade leading to the onset of corneal neovascularization.

Endothelial Growth Factors↗
PubMed2005

Three cases of large retinal capillary hemangiomas treated with verteporfin and photodynamic therapy.

OBJECTIVE: To investigate the efficacy of verteporfin and photodynamic therapy in the treatment of large retinal capillary hemangiomas. METHODS: Case reports of 3 patients with large retinal capillary hemangiomas treated with photodynamic therapy using verteporfin. Standard verteporfin dosages (6 mg/m(2) of body surface area) were given. Both standard and modified photodynamic protocols were followed. Modified protocols included shorter verteporfin infusion times and longer light exposure times. RESULTS: Pretreatment best-corrected Snellen visual acuity of the 3 affected eyes were 20/100, 20/50, and 2/200, respectively. All cases had associated exudative retinal detachments involving the macula. Cases 1 and 2 were classic endophytic retinal capillary hemangiomas. Case 3 was a reactive retinal capillary hemangioma. Case 1 had 2 photodynamic therapy treatments, and after 8 months, visual acuity improved to 20/40. Two years after initiating photodynamic therapy, the visual acuity was 20/30 and there was no reperfusion of the hemangioma. Case 2 had 3 photodynamic therapy treatments. The hemangioma was fibrotic, and 20 months after initiating photodynamic therapy visual acuity improved to 20/30. Case 3 had 1 treatment, 11 weeks later and visual acuity improved to 20/400. Four months after treatment, visual acuity returned to counting fingers because of tractional elevation of the macula as the capillary hemangioma fibrosed. Vitrectomy surgery was performed, and choroidal and retinal neovascularization was discovered. Three months after vitrectomy visual acuity was 20/400. In cases 1 and 2, the capillary hemangioma ultimately regressed, and the exudative detachment resolved. CONCLUSIONS: Verteporfin and photodynamic therapy were effective in achieving closure of large retinal capillary hemangiomas. In all cases, the hemangioma underwent fibrosis with consequent macular puckering due to retinal traction. In all cases, the visual acuity improved.

Adolescent↗
PubMed1998

Immunolocalization of transforming growth factor beta during wound repair in rat retina after laser photocoagulation.

BACKGROUND: Scatter photocoagulation induces regression of retinal neovascularization, but the mechanism of its therapeutic effect is incompletely understood. To elucidate the mechanism of therapeutic effect of photocoagulation is the main focus of our research. We have already demonstrated basic fibroblast growth factor (bFGF) immunolocalization during retinal wound repair following laser photocoagulation. Transforming growth factor beta (TGF beta) reportedly inhibits endothelial cell growth and bFGF-induced cell proliferation in vitro. In the present study, we evaluated the immunohistochemical localization of TGF-beta 1 and -beta 2 during wound repair in the rat retina following laser photocoagulation. METHODS: Krypton laser photocoagulation was performed on the eyes of pigmented rats. The eyes were then enucleated on day 1, 3, 7, 14, 28 or 56 following the photocoagulation and enrolled into the analysis of immunohistochemical localization of TGF-beta 1 and -beta 2. RESULTS: Immunoreactivity for TGF-beta 1 and -beta 2 was present in the ganglion cell layer and photoreceptor outer segments of the normal adult rat retina. The cytoplasm of RPE cells at the photocoagulated lesion showed intense TGF-beta 1 and -beta 2 immunoreactivity on day 3 after laser photocoagulation. Macrophages that migrated into the lesion lacked positive staining for TGF-beta 1 and -beta 2. TGF-beta immunoreactivity in RPE cells continued to be upregulated for more than 1 month compared with that in normal RPE cells. Controls did not exhibit any positive staining. CONCLUSION: An elevated expression of TGF-beta immunoreactivity for a longer period of time than bFGF was observed in RPE cells at the photocoagulated lesion in vivo. In the late phase of retinal wound repair, TGF-beta may inhibit cell proliferation induced by mitogens, introduce an end stage of cellular events, and induce extracellular matrix induction.

Animals↗
PubMed1993

Ocular vascular disease: in-office primary care diagnosis.

Central retinal artery occlusion occurs most commonly between the ages of 50 and 70 years, and nearly one-half (45%) of patients also have carotid artery disease. Other causes of vision-threatening vascular disease include atherosclerosis, embolism, hypertension, diabetes mellitus, and valvular disease. Symptoms vary, depending on the ocular structures involved. The patient's symptoms are an important clue to the diagnosis of peripheral or posterior retinal vascular occlusion, macular blood vessel disease, intravitreal hemorrhage, optic nerve ischemia, and ocular ischemic syndrome. The patient's ocular symptoms should lead to investigation for clinical signs of ocular vascular disease (eg, hemorrhage, "hard" or "soft" exudates, neovascularization, retinal edema, pallor, emboli, vessel narrowing, or atriovenous crossing changes).

Aged↗
PubMed1982

Atypical serpiginous choroiditis.

Patients with serpiginous choroiditis may demonstrate atypical features. In this series 14 (56%) of 53 patients demonstrated either active choroidal neovascularization (13%) or disciform macular scarring (13%). Despite a slight excess of male subjects, five of seven patients with active choroidal neovascularization were female. Three had bilateral disciform disease. All patients with this complication had visual acuity of 6/60 or less. None were able to be successfully treated by photocoagulation. One patient had secondary branch venous obstruction peripherally, associated with retinal neovascularization. Patients with serpiginous choroiditis are at risk of losing central vision from either an acute active lesion in the macula or choroidal neovascularization occurring at the margin of an inactive chorioretinal scar. Serial examination at regular intervals is recommended to rule out the development of possibly treatable choroidal neovascularization in patients with serpiginous choroiditis.

Choroid↗
PubMed2004

Pathogenesis of retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a major cause of blindness in children in developed countries. ROP is a two-phase disease, beginning with delayed retinal vascular growth after premature birth (Phase I). Phase II follows when Phase I-induced hypoxia releases factors to stimulate new blood vessel growth. Both oxygen-regulated and non-oxygen-regulated factors contribute to normal vascular development and retinal neovascularization. Vascular endothelial growth factor (VEGF) is an important oxygen-regulated factor. A critical non-oxygen-regulated growth factor is insulin-like growth factor-I (IGF-I). In knockout mice, lack of IGF-I prevents normal retinal vascular growth, despite the presence of VEGF, important to vessel development. In vitro, low IGF-I levels prevent VEGF-induced activation of Akt, a kinase critical for vascular endothelial cell survival. We found that premature infants who develop ROP have low levels of serum IGF-I compared to age-matched infants without disease. IGF-I is critical to normal vascular development. Low IGF-I predicts ROP in premature infants, and restoration of IGF-I to normal levels might prevent ROP.

Animals↗
PubMed1976

Viscosity and retinal vein thrombosis.

Whole-blood and plasma viscosity with haematological and biochemical investigations were measured in 44 patients with retinal vein occlusion. The patients were subdivided on the basis of fluorescein angiographic findings into: 1. Those with large areas of capillary non-perfusion. 2. Those with small areas of capillary non-perfusion. 3. Those with an intact capillary pattern. Capillary non-perfusion in retinal vein occlusion is associated with a higher morbidity owing to the complications of retinal neovascularization. Significantly higher values of whole-blood viscosity, packed cell volume, and yield stress have been found in patients with capillary non-perfusion than in those without. These differences may be of critical importance during the episode of retinal vein occlusion and suggest an aetiological factor in the development of capillary non-perfusion. Higher whole-blood and plasma viscosity values and plasma fibrinogen levels have also been shown in the whole retinal vein occlusion group compared with a control group of 30 individuals. These differences may be a factor in the development of retinal vein occlusion but their precise role is difficult to evaluate. Further biochemical investigations in the vein occlusion group supported the strong association with arterial disease and suggested a higher incidence of biochemical abnormalities in those patients with capillary non-perfusion.

Adult↗
PubMed2003

Coordinate activation of HIF-1 and NF-kappaB DNA binding and COX-2 and VEGF expression in retinal cells by hypoxia.

PURPOSE: Proinflammatory signaling mechanisms are implicated in the induction of retinal neovascularization (NV) during ischemic retinopathies. This study examined transcription factor (TF) AP-1, HIF-1, and NF-kappaB DNA-binding in relation to cyclooxygenase (COX)-2 and VEGF RNA and protein levels in hypoxia-triggered monkey choroidal retinal (RF/6A) endothelial cells. Effects of the carboxamide CGP43182 were tested on COX-2 and VEGF activation and prostaglandin (PG)E(2) release. METHODS: RF/6A cells were subjected to hypoxia for 1 and 3 hours, at which times RNA and proteins were isolated. Potential AP-1, hypoxia-inducible factor (HIF)-1 and NF-kappaB DNA-binding sites were identified using DNA sequence search algorithms and were analyzed using gel-shift assay. COX-2 and VEGF RNA, protein, and PGE(2) levels were quantified by RT-PCR, Western analysis, and enzyme immunoassay, respectively. Tubular morphogenesis was analyzed with phase-contrast imaging microscopy. RESULTS: Nuclear AP-1, HIF-1 and NF-kappaB promoter DNA binding increased 1.5-, 4-, and 3-fold, respectively, after 1 hour of hypoxia. COX-2 RNA was elevated five- and fourfold after 1 and 3 hours of hypoxia, respectively. VEGF RNA and protein abundance lagged behind COX-2 induction but were each increased two- to threefold 3 hours after hypoxia. CGP43182 was found to inhibit NF-kappaB DNA binding, COX-2 and VEGF gene expression, PGE(2) release, and hypoxia-induced tubular morphogenesis. CONCLUSIONS: Maximum HIF-1 and NF-kappaB DNA binding immediately before COX-2 expression suggests that these TFs are important regulators of COX-2 induction in hypoxic RF/6A cells. IL-1beta emulated AP-1, HIF-1, and NF-kappaB DNA binding during hypoxia and may be a novel cytokine trigger for NV. CGP43182 appears to be an effective inhibitor of NV. VEGF expression appears to be regulated through dual interdependent mechanisms involving HIF-1 directly and indirectly through NF-kappaB-mediated COX-2 expression and PGE(2) production.

Animals↗
PubMed1988

Oxygen-induced retinopathy in newborn rats: effects of prolonged normobaric and hyperbaric oxygen supplementation.

An experimental study was conducted to verify the effects of prolonged normobaric and hyperbaric oxygen supplementation on retinal vessels in newborn animals. Nine litters of newborn Wistar rats were used in the following way. Two litters were used as controls. Two other litters received normobaric oxygen supplementation (FiO2 80%) for five days after birth. These rats were then removed and kept for five more days in room air. Retinopathy with marked peripheral retinal neovascularization was seen in these litters. Three other litters were exposed to the same treatment for ten days after birth, removed from oxygen, and kept for 15 more days in room air. Severe retinopathy with extraretinal proliferation and, in some cases, retinal detachment developed in these animals. Two other litters received hyperbaric (1.80 atm) oxygen supplementation (FiO2 80%) for ten days after birth and were then kept for 15 days in normobaric room air. These animals showed no evidence of peripheral retinopathy. It is possible that moderate hyperbarism exerts, in the newborn rat, a protective action against the toxic effects of oxygen supplementation on immature retinal vessels.

Animals↗
PubMed2006

Proangiogenic effects of protease-activated receptor 2 are tumor necrosis factor-alpha and consecutively Tie2 dependent.

OBJECTIVE: Angiogenesis is essential physiologically in growth and pathologically in tumor development, chronic inflammatory disorders, and proliferative retinopathies. Activation of protease-activated receptor 2 (PAR2) leads to a proangiogenic response, but its mechanisms have yet to be specifically described. Here, we investigated the mode of action of PAR2 in retinal angiogenesis. METHODS AND RESULTS: PAR2-activating peptide, SLIGRL, increased retinal angiogenesis associated with an induction of vascular endothelial growth factor and angiopoetin-2 and most notably tie2 in the retina in vivo as well as in cultured neuroretinal endothelial cells. SLIGRL also induced release of the proinflammatory and angiogenic mediator tumor necrosis factor-alpha (TNF-alpha) via the MEK/extracellular signal-regulated kinase (ERK) (MEK/ERK) pathway in these endothelial cells. TNF-alpha, in turn, elicited tie2 expression by activating the MEK/ERK pathway. PAR2-evoked tie2 expression, endothelium proliferation (in vitro), and retinal neovascularization (in vivo) were abrogated by selective TNF-alpha blockers (neutralizing antibody infliximab and soluble TNF-alpha receptor-Fc fusion protein etanercept) as well as the MEK inhibitor PD98059. CONCLUSIONS: The proangiogenic properties of PAR2 are intertwined with its proinflammatory effects, such that in retinal vasculature, they depend on TNF-alpha and subsequent induction of tie2 via the MEK/ERK pathway.

Angiopoietin-2↗
PubMed1990

Müller cell changes precede vascularization of the pigment epithelium in the dystrophic rat retina.

In the Royal College of Surgeons rat with inherited retinal dystrophy, photoreceptor cell degeneration is accompanied by retinal pigment epithelial (RPE) cell alterations and Müller cell changes such as increased expression of glial fibrillary acidic protein (GFAP). Vascular changes such as vascularization of the RPE, vascular proliferation, and formation of vitreoretinal membranes (VRMs) are observed later. To study the relationship of Müller cell changes to the vascular alterations in the dystrophic retina, we used immunoperoxidase techniques and antibodies against GFAP and vimentin. Our study showed that during photoreceptor degeneration, Müller cells expressed small amounts of GFAP. As degeneration progressed, GFAP expression increased and morphological alterations occurred in Müller cells. Müller cell apical processes extended and proliferated in the subretinal space and contacted the apical surface of duplicated RPE cells. Later, GFAP reactive fibers surrounded retinal vessels apposed to the RPE. As the vessels became enmeshed within the RPE, the GFAP-positive perivascular processes disappeared. Eventually, the RPE-associated vessels became displaced into the inner retina where VRMs were sometimes observed. Immunoblots showed increased GFAP in dystrophic as compared with control retinas. Studies of vimentin distribution in the dystrophic retina showed results similar to the GFAP study. Moreover, the vimentin study suggested increased number of Müller cell processes in the dystrophic as compared with control retinas. The close temporal and anatomical relationships among Müller cell, RPE, and vascular changes in the dystrophic rat suggest a role for Müller cells in retinal neovascularization and proliferative retinopathy.

Animals↗
PubMed2003

Expression of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in sickle cell retina and choroid.

Pigment epithelium-derived factor (PEDF) has been shown to be an inhibitor of angiogenesis as well as a multipotent neurotrophic factor in the mammalian eye. Changes in PEDF levels have been correlated with development of retinal neovascularization in oxygen-induced retinopathy. The purpose of this study was to determine the localization and relative level of PEDF in human retinas and choroids using immunohistochemistry and evaluate the changes in PEDF and vascular endothelial growth factor (VEGF) localization and their relation to the progression of proliferative sickle cell retinopathy. Cryopreserved tissues from eyes of normal subjects and subjects with non-proliferative or proliferative sickle cell retinopathy were used with streptavidin peroxidase immunohistochemistry. A rabbit polyclonal antibody was made against recombinant human PEDF. Binding of the antibody was blocked by preincubation of the antibody with excess human recombinant PEDF. Relative levels of immunoreactivity were scored with a seven-point grading system and by microdensitometric analysis.The most prominent sites of PEDF localization in the normal eye were the vitreous condensed at the internal limiting membrane and RPE-Bruch's membrane-choriocapillaris complex. PEDF was also prominent in choroidal stroma. There was limited immunoreactivity in some cells of the neural retinas, in blood vessels and in the interphotoreceptor matrix (IPM). There was no difference in ratio (1.47 vs. 1.44) of PEDF/VEGF or the relative levels of either growth factor in the retinal vasculatures of the control subjects and perfused area of non-proliferative sickle cell retinas. The ratio was increased in the non-perfused area of the non-proliferative sickle cell retinas (2.24). In eyes with proliferative sickle cell retinopathy, elevated PEDF and VEGF immunostaining was present in viable vessels of sea fan neovascular formations as well as feeder vessels of sea fans. The PEDF/VEGF ratio in sea fans was 1.0. Immunoreactivity for PEDF was prominent in retinal vessels in non-perfused regions and in atrophic sea fans, while VEGF immunoreactivity was weak or absent in these structures. In conclusion, PEDF and VEGF were both significantly elevated in viable sea fan formations in sickle cell disease (p<0.05) but only PEDF was present in non-viable sea fans. The highest levels of PEDF in all eyes were associated with extracellular matrices (vitreous, choroidal stroma, IPM, and walls of blood vessels). PEDF might play an important role in inhibiting angiogenesis and inducing the regression of sea fans. Progression of angiogenesis may be dependent on the ratio of PEDF/VEGF.

Adolescent↗
PubMed2002

Pathogenesis of retinopathy of prematurity.

UNLABELLED: Retinopathy of prematurity (ROP) is a blinding disease, initiated by delayed retinal vascular growth after premature birth. There are both oxygen-regulated and non-oxygen-regulated factors, which contribute to both normal vascular development and retinal neovascularization. One important oxygen-regulated factor, critical to both phases of ROP, is vascular endothelial growth factor (VEGF). A critical non oxygen-regulated growth factor is insulin-like growth factor (IGF-1). In knockout mice, lack of IGF-1 prevents normal retinal vascular growth, despite the presence of VEGF, important to vessel development. In vitro, low IGF-1 prevents vascular endothelial growth factor-induced activation of Akt, a kinase critical for vascular endothelial cell survival. Premature infants who develop ROP have lower levels of serum IGF-1 than age-matched infants without disease. CONCLUSION: IGF-1 is critical to normal vascular development. Low IGF-1 predicts ROP and restoration of IGF-1 to normal levels may prevent ROP.

Animals↗