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Isolated fetal choroid plexus cysts: role of ultrasonography in establishment of the risk of trisomy 18.

OBJECTIVE: The significance of isolated choroid plexus cysts found by ultrasonographic scan during the second trimester as a marker for trisomy 18 is still debated. We analyzed our data and reviewed the series published in the English-language literature to calculate the likelihood ratio of trisomy 18 in the presence of isolated choroid plexus cysts; that is, the factor by which the individual risk of trisomy 18 is increased in the presence of isolated choroid plexus cysts. STUDY DESIGN: Likelihood ratios were calculated as ratio of the sensitivity to the false-positive rate. Sensitivity was defined as the rate of isolated choroid plexus cysts detected at midgestation among fetuses with trisomy 18. False-positive rate was defined as the rate of choroid plexus cysts detected at midgestation in the population without trisomy 18. The sensitivities of all published series reporting rates of choroid plexus cysts at the time of the first ultrasonographic examination between 14 and 24 weeks' gestation in populations with trisomy 18 and in low-risk populations were included in the analysis. To these we added all cases of trisomy 18 diagnosed at our institution during the period January 1, 1988, through June 30, 1998, in which prenatal ultrasonographic examination was performed between 14 and 24 weeks' gestation. RESULTS: The prevalence of second-trimester ultrasonographic detection of isolated choroid plexus cysts among fetuses with trisomy 18 was 6.7% (13/194), whereas that in the population without trisomy 18 was 0.9% (752/79,583). The likelihood ratio associated with isolated choroid plexus cysts was therefore 7.09 (95% confidence interval, 3.97-12.18). CONCLUSION: The presence of isolated second-trimester choroid plexus cysts increases the base risk of trisomy 18 by a factor of 7.09. This likelihood ratio can be multiplied by the risk calculated according to maternal age to obtain the individual risk of trisomy 18 and thus permit more accurate counseling of the patient.

Adult↗

Evaluation of the dynamics of choroidal circulation in experimental acute hypertensionusing indocyanine green-stained leukocytes.

PURPOSE: To evaluate the dynamics of choroidal circulation in experimental acute hypertension, using the indocyanine green leukocyte angiography (ILA) method, which the authors have developed for the evaluation of leukocyte dynamics in choroidal circulation. METHODS: Japan White rabbits were used in the present study. Leukocytes were collected by centrifugal separation of the autologous blood, and were stained with indocyanine green (ICG) dye. The ICG-stained leukocyte fluid was injected into an ear vein, and fundus images were obtained by infrared laser and a scanning laser ophthalmoscope. Experimental acute hypertension was induced by the intravenous drip injection of angiotensin II (AII). RESULTS: The fluorescent dots rapidly moved in choroidal arteries at a decreasing velocity, passed very slowly through choroidal capillaries and drained into choroidal veins. Under normal blood pressure, the mean leukocyte velocities in arteries, capillaries and veins were 8.63+/-1.68, 0.52+/-0.07, and 6.96+/-2.20 mm/s, respectively. On the other hand, the respective mean velocities in acute hypertension induced by AII were 13.50+/-1.82, 0.81+/-0.09, and 10.54+/-3.91 mm/s. Besides flow velocity, no change in leukocyte dynamics was observed. CONCLUSIONS: Under the condition of acute hypertension induced by AII, leukocytes moved faster in the total choroidal circulation (from arteries to veins) compared to their velocity under the condition of normal blood pressure. Blood velocities might increase in the total choroidal circulation at an early stage in acute hypertension induced by AII, resulting in increased choroidal blood flow. ILA makes it possible to evaluate the changes in choroidal circulation under various pathologic conditions.

Acute Disease↗

The isolated choroid plexus cyst.

OBJECTIVE: To describe the karyotypes of a population of fetuses with choroid plexus cysts and compare affected fetuses with and without additional ultrasonographic findings. METHODS: The study population included all patients undergoing second-trimester ultrasound examination in a prenatal diagnostic program between January 1993 and October 1995. The records of all cases in which a choroid plexus cyst was found were reviewed, and information was abstracted regarding the fetal karyotype and the presence of other sonographic abnormalities. RESULTS: Two hundred ten cases of choroid plexus cysts were identified among 7617 patients (2.8%) who underwent second-trimester ultrasound examination. The majority of the cases (181, or 86%) involved isolated choroid plexus cysts and the remaining 29 (14%) were associated with additional ultrasonographic findings. Autosomal aneuploidy was found in one patient with an isolated choroid plexus cyst (trisomy 21) and in another with additional findings (trisomy 18); the mothers of both of these patients were at least 35 years old. For those fetuses with known outcome, the risk of aneuploidy with isolated choroid plexus cyst (one in 180) was not statistically significantly different from that associated with choroid plexus cyst accompanied by other sonographic findings (one in 26). More than 1000 fetuses with choroid plexus cysts would have to be studied to determine whether such a difference was real. CONCLUSION: Because of the rarity of aneuploidy, the reported risk for a fetus with an isolated choroid plexus cyst must be interpreted cautiously and should include the baseline risk.

Brain Diseases↗

Changes in choroidal blood flow during light/dark transitions are not altered by atropine or propranolol in healthy subjects.

It has recently been reported that light/dark transitions lead to changes in choroidal blood flow. Several observations indicate that these changes in choroidal perfusion are triggered at least in part by neural mechanisms. In the present study we hypothesised that the choroidal blood flow response to changes in retinal illumination may be modified by either the muscarinic receptor antagonist atropine or by the beta-receptor antagonist propranolol. In 15 healthy subjects the response of choroidal perfusion was studied in a randomised placebo-controlled three way cross-over study using laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude. Before drug administration a transition from light to dark reduced both choroidal haemodynamic parameters by 8%-12%. Neither propranolol nor atropine altered basal choroidal blood flow or choroidal blood flow responses to light/dark transitions. Our data indicate that neither muscarinic nor beta-receptors are involved in the choroidal blood flow response to changes in retinal illumination. Further studies are required to elucidate which mechanisms contribute to this blood flow behaviour of the choroid.

Adaptation, Ocular↗

The effect of external eye irradiation on choroidal circulation.

BACKGROUND: The effect of external beam radiation therapy (teletherapy) on the choroidal circulation is poorly known. Eyes irradiated with teletherapy represent a good model to study, without confounding factors, the pathophysiologic and clinical aspects of radiation-induced chorioretinal damage. This study used fluorescein and indocyanine green choroidal angiography to investigate the late effects of external eye irradiation on the choroidal circulation. METHODS: Fluorescein angiography and indocyanine green choroidal videoangiography were performed on patients with radiation retinopathy because of external eye irradiation for orbital and paranasal sinus malignancies. Patients were divided into two groups according to the treatment field (anterior unilateral or bilateral). RESULTS: Indocyanine green angiograms showed areas of choriocapillaris hypoperfusion in all eyes-unilateral or bilateral irradiation-affected by radiation retinopathy. Late indocyanine green choroidal staining was found in five eyes (28%) of the patients who received unilateral anterior irradiation. In the same group, nine eyes (52%) had signs of choroidal precapillary occlusion and four eyes (23%) had rubeosis iridis without retinal neovascularization. One case of subfoveal choroidal neovascularization was documented in the bilateral irradiation group. CONCLUSIONS: Radiation side effects are not limited to the retinal vessels but also involve choroidal circulation. The damage to the choroid is primarily vascular, and its clinical aspects depend on the treatment fields. Anterior irradiation may be a critical factor for the appearance of unusual rubeosis iridis and neovascular glaucoma.

Adolescent↗

Nerve growth factor regulates human choroidal, but not retinal, endothelial cell migration and proliferation.

We have previously shown that sympathetic denervation results in significant blood vessel growth of the choroid and retina. The mechanism of this growth remains unclear. Since sympathetic denervation can result in increased nerve growth factor (NGF) levels, it was the goal of this study to determine if choroidal and retinal endothelial cells in culture would respond to nerve growth factor and if nerve growth factor promote endothelial cell migration and proliferation, two components of angiogenesis. Western blotting with phospho-specific antibodies, cell migration, and cell proliferation assays were employed to determine NGF effects on both choroidal and retinal cell growth. NGF treatment produced phosphorylation of TrkA in choroidal and retinal endothelial cells. NGF stimulation resulted in activation of ERK1/2, Akt, and Src in choroidal endothelial cells, while little phosphorylation was noted following NGF treatment in retinal endothelial cells. NGF increased choroidal endothelial cell migration by 50% over control and this was inhibited by pretreatment with LY294002 (PI3K inhibitor), Akt inhibitor, and MMP2/9 inhibitor. KT5823, PD98059, and PP2 did not affect choroidal cell migration. NGF also produced a 47% increase in choroidal endothelial cell proliferation, which was blocked by PP2, LY294002, Akt inhibitor, KT5823, and PD98059. NGF stimulation did not alter retinal endothelial cell migration or proliferation. Thus, it appears that increased NGF levels that may be noted after sympathectomy are capable of producing some aspects of vascular remodeling via different signaling cascades in choroidal endothelial cells in culture.

Cell Division↗

In vivo choroidal circulation and its watershed zones.

In vivo studies on choroidal vascular bed have shown that the posterior ciliary arteries (PCAs) right down to their terminal arterioles in the choroid have strictly segmental blood flow and they behave as end-arteries. These studies totally contradict the picture shown by all the postmortem cast studies of the choroidal vascular bed as a freely communicating system. The in vivo pattern helps to explain the typically localised nature of inflammatory, ischaemic, degenerative and metastatic nature of the choroidal lesions. Like other end-arterial vascular systems in the body, the choroidal vascular bed has watershed zones situated between the various PCAs, the short PCAs, the choroidal arteries, the arterioles, and the vortex veins. The end-arterial nature of the choroidal vasculature and the existence of watershed zones in the choroid are of great clinical importance; their role in the production of various ischaemic lesions in the choroid, anterior ischaemic optic neuropathy (AION) and other ischaemic disorders of the optic nerve head is discussed.

Animals↗

Indocyanine green angiographic features of traumatic choroidal ruptures.

PURPOSE: To investigate the indocyanine green (ICG) angiographic findings of healed traumatic choroidal ruptures. METHODS: Three eyes of two patients with choroidal ruptures underwent both fluorescein angiography and ICG angiography with a digital high-resolution system. RESULTS: Fundus examination showed healed choroidal ruptures in all three eyes. Two of the eyes had old macular scars and one eye had a recent choroidal neovascular membrane with serous detachment of the macula. On fluorescein angiography, the choroidal ruptures showed hypofluorescence at very early stages followed by late hyperfluorescence. On ICG angiography, the choroidal ruptures were hypofluorescent in early, mid and late phases. ICG angiography provided a clear delineation of the choroidal ruptures. In all eyes, the lesion was better defined on the ICG angiogram than on the fluorescein angiogram. CONCLUSIONS: ICG angiography can be helpful in the clinical evaluation of choroidal ruptures and can be used together with fluorescein angiography for the diagnosis and follow-up of choroidal ruptures.

Adult↗

Role of adrenergic receptors in vascular remodelling of the rat choroid.

1. Choroidal blood vessels, located between the sclera and retina, constitute the principle source of blood flow to ocular structures. The choroid is innervated by vasoconstrictor sympathetic and vasodilator parasympathetic nerves. 2. We have shown previously that sympathetic denervation for 6 weeks leads to significant increases in choroidal thickness, percentage of choroid occupied by vascular lumina, and numbers of choroidal venules, large arterioles and outer retinal capillaries. Sympathetic deafferentation produces similar increases, indicating that loss of sympathetic nerve activity is responsible for increased vascularity after sympathectomy. Thus, sympathetic neurotransmission normally may be important in suppressing vascular proliferation in the adult rodent eye. 3. The aim of the present study was to determine whether sympathetic nerves act by way of adrenergic receptors to maintain normal choroidal vascular integrity. 4. The alpha-adrenoceptor antagonist, phentolamine (1 mg kg(-1) day(-1)), the beta-receptor antagonist, propranolol (1 mg kg(-1) day(-1)), or saline vehicle was infused for 3 weeks using subcutaneously implanted osmotic minipumps. 5. In phentolamine treated rats, no significant changes were noted relative to saline infused controls. However, propranolol treatment resulted in increases in choroidal thickness, vascular luminal area, and numbers of large choroidal venules and both small and large arterioles, approximating the remodelling seen after chronic sympathectomy. 6. We conclude that sympathetic nerves play a role in maintaining normal choroidal vascular architecture through actions mediated primarily by beta-adrenoceptors.

Adrenergic Antagonists↗

Effect of nitric oxide synthesis inhibition on post-occlusive choroidal blood flow in rats.

Experiments were designed to study involvement of nitric oxide on vascular responses to ocular ischemia in the anesthetized rat. Anterior choroidal blood flow was measured using laser-Doppler flowmetry. In some experiments, cerebral cortical blood flow also was measured. Ischemia was produced by either occlusion of the cephalic blood supply or more locally via a ligature tightened around the eye stalk. Arterial blood pressure and choroidal blood flow was continuously measured before, during and after a 20 min ischemic challenge. Both methods of ischemia reduced choroidal blood flow (>90%) with no consistent ocular hyperemia seen upon reperfusion. No significant differences in response pattern between the two ischemia techniques were apparent. Treatment with the non-selective inhibitor of nitric oxide (L-NAME 2 mg/kg, i.v.) did not alter either basal choroidal blood flow or the pattern of reperfusion. A larger dose of L-NAME (50 mg/kg, i.v.) reduced both basal choroidal blood flow and the final reperfusion level (most likely due to continued depression of the basal ocular choroidal blood flow). Neither D-NAME nor the neuronal nitric oxide synthase inhibitor, 7-nitroindazole, altered basal anterior choroidal blood flow or the reperfusion pattern seen after reperfusion. The results confirm our previous observations that inhibition of endothelial nitric oxide lowers. basal choroidal blood flow in the rat eye. However, in contrast to the cerebral circulation where L-NAME greatly attenuates initial reperfusion to the cerebral cortex, inhibition of nitric oxide synthase does not appear to notably further influence anterior choroidal reperfusion.

Animals↗

Choroid plexus protects cerebrospinal fluid against toxic metals.

Although heavy metal ions are known to be toxic to the central nervous system (CNS), the mechanisms by which the CNS may protect itself from initial challenges of such toxic ions is unknown. The choroid plexus is the principal site of formation of the cerebrospinal fluid (CSF) which bathes the brain. We have determined in rats and rabbits that after intraperitoneal administration of lead, cadmium, mercury, and arsenic compounds, these toxic metal ions accumulated in the lateral choroid plexus at concentrations of Pb, Hg, and As that were 70-, 95-, and 40-fold higher, respectively, than those found in the CSF. Cd was not detected in the CSF. In addition, concentrations of these heavy metal ions were found to be many fold greater in the choroid plexus than in the brain or blood. The accumulation of Pb in the choroid plexus was dose-dependent and time-related. When the choroid plexus was preincubated, in vitro, with ouabain (1.5 mM), the uptake of Cd from the CSF side of the choroid plexus was inhibited 57%. Cadmium metallothionein was not found in the choroid plexus. Whereas the concentration of reduced glutathione in the choroid plexus was less than that in the brain cortex, the concentration of cystine was fourfold greater. The lateral choroid plexus sequesters Pb, Cd, As, and Hg. It appears to be one of the important mechanisms that protects the CSF and the brain from the fluxes of toxic heavy metals in the blood.

Animals↗

In situ formation of immune complexes in the choroid plexus of rats by sequential injection of a cationized antigen and unaltered antibodies.

The deposition of cationized human serum albumin (HSAED) in the choroid plexus of rats was compared to deposition in renal glomeruli. Initial deposition in the choroid plexus required a higher dose of antigen than deposition in glomeruli. The optimal dose for deposition in the choroid plexus was 50 mg/kg of HSAED. With this dose the antigen was still present in the choroid plexus at eight days after injection, whereas the glomeruli became largely negative by one day. Immune complex formation and persistence was examined in the choroid plexus by injecting rabbit antibodies to HSA at varying times after the injection of HSAED. When a limited amount of antibody was injected, it localized preferentially to glomeruli as compared to the choroid plexus. When sufficient antibodies were injected, the antigen and antibodies persisted in a comparable manner in the choroid plexus and glomeruli. By the eighth day after injection of foreign proteins, rat IgG deposited in both organs, indicating an endogenous immune response. The formed deposits were still present at 28 days, containing HSA, rabbit IgG, and rat IgG, but not rat C3. These results indicate that immune deposits readily form in the choroid plexus after injecting a cationized antigen. Differences, however, exist in the formation of immune deposit in the choroid plexus and the glomeruli.

Animals↗

Surgical drainage of choroidal effusions following glaucoma surgery.

PURPOSE: To determine the efficacy and safety of surgical drainage of choroidal effusions that occurs following glaucoma surgical procedures. PATIENTS AND METHODS: Ninety-four choroidal drainage procedures performed at a single institution from 1986 to 2001 were reviewed retrospectively. Sixty-three eyes of 63 persons who underwent one or more drainage procedures for choroidal effusions that developed following glaucoma surgical procedures were identified. Eyes diagnosed with suprachoroidal hemorrhage prior to intervention were excluded. The cases were evaluated for resolution of choroidal detachment, post-drainage complications, visual acuity, and intraocular pressure before and after drainage. RESULTS: Indications for choroidal drainage included flat anterior chamber (25 eyes), decreased vision (22 eyes), and persistent choroidal detachment (16 eyes). Complete resolution of choroidal effusions was achieved in 37 (59%) eyes by 1 month, 51 (81%) eyes by 2 months, and in 57 (90%) eyes by 4 months following the initial drainage procedure. Overall success rate per procedure at 12 months was 77% (60/78). Compared with pre-drainage, intraocular pressure was higher at 6 and 12 months post-drainage (P < 0.0001) and visual acuity was better at 6 and 12 months post-drainage (logMAR, P < 0.0001). Twenty-seven (77%) of 35 phakic eyes developed cataracts during the 12 months post-drainage. CONCLUSIONS: Choroidal effusions that develop after glaucoma surgery can usually be drained with minimal complications. Surgical drainage is associated with improved vision and resolution of hypotony. Cataracts may progress following choroidal drainage but this may be due to the pre-drainage hypotony conditions.

Adult↗

Distribution and characterisation of rat choroidal mast cells.

Despite the implication that choroidal mast cells are involved in the onset of experimental autoimmune uveoretinitis (EAU), a widely used animal model of uveoretinitis, little is known of these cells. In the present study the distribution, total number, regional density, and phenotype of choroidal mast cells were examined in Lewis, Wistar Furth, PVG/c, and brown Norway rats. Choroidal mast cells were predominantly associated with arteries and arterioles of more than 30 microns diameter which lie in the outer (sclerad) choroid. The density of mast cells was greatest in the posterior choroid with density diminishing anteriorly. The choroid of male Lewis rats contained significantly greater number of mast cells than that of females (p < 0.01). Histochemical (Alcian blue/safranin) and immunohistochemical (anti-rat mast cell protease I and II monoclonal antibodies) studies revealed choroidal mast cells were of the connective tissue type. However, granule proteinase content appeared less than that of well characterised connective tissue mast cell populations such as those in mesentery and skin. Lewis rats exhibited the highest density of choroidal mast cells (23.6 (SD 1.2)/mm2), Wistar Furth approximately half that of Lewis (13.5 (0.7)/mm2) while PVG/c and brown Norway rats had very low densities (3.06(0.3); 1.95(0.2/mm2 respectively). These studies provide valuable choroidal mast cell data for rats which may have implications for our understanding of experimental models of intraocular inflammation and clinical uveitis.

Animals↗

Regulation of prostanoid vasomotor effects and receptors in choroidal vessels of newborn pigs.

This study was conducted to determine if high perinatal prostaglandin (PG) and thromboxane (TxA2) levels modified their choroidal vasomotor effects and receptor levels. Both nonperfused (eyecup preparations) and perfused choroidal vessels from saline- or ibuprofen-treated 1-day-old pigs and tissues from adult pigs were used; all prostanoids produced similar vasomotor effects on both preparations. Choroidal PGF2alpha, TxA2, PGI2, and PGD2 levels were higher in the newborn than in adult pigs; injections of ibuprofen (40 mg/kg every 4 h for 48 h) into newborn pigs significantly decreased choroidal levels of all these prostanoids. PGF2alpha and the TxA2 mimetic U-46619 caused less choroidal vasoconstriction and production of inositol 1,4,5-trisphosphate (IP3) in the newborn than in adult pigs. Ibuprofen treatment increased choroidal PGF2alpha vasoconstrictor effects, IP3 production, and receptors, but did not modify response to U-46619. Carbaprostacyclin (PGI2 analog) caused a greater choroidal vasodilatation and adenosine adenosine 3',5'-cyclic monophosphate (cAMP) production in the newborn than in adult pigs; these effects were not modified by ibuprofen. PGD2 did not increase cAMP but caused greater dilatation and nitrite [oxidation product of nitric oxide (NO)] production in the choroid of newborn than of adult pigs, which were decreased to adult levels by ibuprofen and the NO synthase inhibitor N(omega)-nitro-L-arginine. These data suggest that high perinatal PG levels downregulate PGF2alpha receptors and vascular effects but do not modify choroidal responses to TxA2 and PGI2; NO seems to contribute to the vasodilator effects of PGD2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Choroid plexus tumors in children: immunohistochemical and scanning-electron-microscopic features.

The 30 choroid plexus tumors recorded in a large pediatric tumor registry were reviewed. The 22 choroid plexus papillomas and 8 choroid plexus carcinomas represented 2.1% of all brain tumors in the registry. The patients (19 boys, 11 girls) were aged 3 months to 12 years (mean: 2 years 9 months). All tumors and four samples of normal choroid plexus were examined with conventional histology, 9 tumors were examined with electron microscopy and 24 using immunohistochemical techniques with antisera against glial fibrillary acidic protein, S-100 protein, epidermal cytokeratin, internal organ cytokeratin and carcinoembryonic antigen. Seven of the tumors (1 carcinoma and 6 papillomas) had some positive cells with antiserum against glial fibrillary acidic protein. Twenty-seven of the tumors (90%) and all normal choroid plexus samples were positive with antiserum to S-100 protein. Some tumor cells from both types of tumor and the normal choroid plexus reacted positively with internal organ cytokeratin antiserum, but all tissue samples were nonreactive with epidermal cytokeratin antiserum. Ultrastructurally, both papillomas and carcinomas displayed cytoplasmic intermediate filaments. Transmission and/or scanning electron microscopy revealed cilia in all choroid plexus papillomas. Frequently, the cilia had an abnormal arrangement, varying from 5 + 0 to 8 + 1. This study demonstrates that tumor cells of choroid plexus origin are characterized by the presence of S-100 protein and internal organ cytokeratin antiserum. Cilia, either normal or abnormal, are consistently identified in papillomas but rarely and with difficulty in carcinomas. Carcinoembryonic antigen is seen in choroid plexus carcinomas but not papillomas.

Adolescent↗

Role of endothelin-1 in choroidal blood flow regulation during isometric exercise in healthy humans.

PURPOSE: There is evidence that the choroid has some autoregulatory capacity in response to changes in ocular perfusion pressure (OPP). The mediators of this response are hitherto unidentified. The hypothesis for the current study was that endothelin (ET)-1 and/or angiotensin (ANF)-II may be involved in choroidal vasoconstriction during an increase in OPP. METHODS: To test this hypothesis a randomized, double-masked, placebo-controlled, three way crossover study was performed in 12 healthy male volunteers. Subjects received on different study days intravenous infusions of the specific ET(A) receptor antagonist BQ-123, the angiotensin converting enzyme inhibitor enalapril or placebo. During these infusion periods subjects were asked to squat for 6 minutes. Choroidal blood flow was measured using a confocal laser Doppler flowmeter and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. RESULTS: BQ-123 and enalapril had no effect on basal blood pressure, pulse rate, intraocular pressure, or choroidal blood flow. During isometric exercise, a pronounced increase in mean arterial pressure paralleled by an increase in OPP was observed. Although choroidal blood flow slightly increased during squatting, the increase was much less pronounced than the increase in OPP, indicating some regulatory potential of the choroid. Enalapril did not alter the choroidal pressure-flow relationship during isometric exercise, but BQ-123 induced a significant leftward shift of the pressure-flow curve (P < 0.001). CONCLUSIONS: The present data indicate that ET-1, but not ANG II, plays a role in choroidal blood flow regulation during isometric exercise in healthy humans. Hence, impaired choroidal autoregulation in patients with ocular vascular diseases may arise from an altered endothelin system. Further studies in such patients are warranted to verify this hypothesis.

Adult↗

VEGF expression and receptor activation in the choroid during development and in the adult.

PURPOSE: Previous studies have demonstrated a role for the retinal pigment epithelium (RPE) in the development and maintenance of the choroidal vasculature, suggesting that RPE serves a trophic role for the choroidal vessels. The goal of this study was to determine the expression pattern of vascular endothelial growth factor (VEGF) and its receptors and their activation status in embryonic and adult choroid, with the purpose of providing cues regarding the role of VEGF in development and stabilization of the choroidal vasculature. METHODS: Transgenic VEGF-LacZ mice were used to examine VEGF expression in embryonic and adult eyes. Expression of VEGF isoforms and receptors in the RPE-choroid complex was assessed by RT-PCR and real-time PCR. VEGF receptor 2 expression was assessed by immunohistochemistry and its activation state was examined by immunoprecipitation followed by phosphotyrosine blot. RESULTS: VEGF is expressed by RPE throughout the choroidal vascular development and in the adult. The major VEGF isoforms detected in adult RPE were VEGF120 and VEGF164, with almost no detectable VEGF188. RT-PCR analysis showed expression of VEGF receptors and coreceptors in the RPE-choroid complex. VEGFR2 was detected in the choriocapillaris underlying the RPE. Immunoprecipitation and phosphotyrosine blot of this receptor revealed that VEGFR2 is activated in adult mouse and bovine choroids. CONCLUSIONS: The observations suggest that VEGF signaling is involved, not only in choroidal vessel formation, but perhaps also in the maintenance of the choriocapillaris.

Animals↗