The congenital unilateral retinocephalic vascular malformation syndrome (bonnet-dechaume-blanc syndrome or wyburn-mason syndrome): review of the literature.

Retinal arteriovenous malformations represent a rare syndrome in which a direct connection of major vessels without interposition of capillaries may lead to various complications such as thrombosis and vessel occlusion. This review comprises the computer-stored data of all the 121 patients with arteriovenous malformations described in the literature. Twenty-seven patients had typical Bonnet-Dechaume-Blanc syndrome (in this article designated as congenital retinocephalofacial vascular malformation syndrome), 25 had incomplete congenital retinocephalofacial vascular malformation syndrome (without facial skin lesions), 57 had isolated retinal arteriovenous malformations, and 12 had arteriovenous communications of the retina and distinct neurological signs, but without neuroradiological evidence of cerebral arteriovenous malformations (presumed cerebral arteriovenous malformations). Concerning the retinal findings, we found a distinct difference by comparing patients with congenital retinocephalofacial vascular malformation syndrome and those with isolated retinopathy without cerebral or facial malformations: extensive retinal malformations of vessels of most parts of the fundus occurred conspicuously more often in patients with retinal and cerebral arteriovenous malformations. In contrast, local retinal arteriovenous malformations occurred in all patients with isolated retinopathy without cerebral or facial malformations and rarely in patients with congenital retinocephalofacial vascular malformation syndrome. In conclusion, patients with arteriovenous communications of the retina should be examined early with brain and orbital neuroimaging to rule out cerebral arteriovenous malformations. Current therapeutic strategies include endovascular, surgical, and radiation procedures.

Septin expression in proliferative retinal membranes.

We undertook this study to evaluate the expression of septin family members SEPT5, SEPT8, and SEPT11 in proliferative retinal membranes. Epiretinal membranes (ERM) were obtained from seven patients with proliferative vitreoretinopathy (PVR) and from four patients and four postmortem eyes with proliferative diabetic retinopathy (PDR). Subretinal membranes (SRM) were obtained from one patient and six postmortem eyes. Membranes were examined by immunohistochemical staining of paraffin sections using polyclonal antibodies against SEPT5, SEPT8, and SEPT11 and an ABC detection system. SEPT8 expression was detected in all ERM and SRM, with an exceptionally strong expression of 100% for ERM of PVR, 63% for PDR membranes, and 57% for SRM. SEPT11 was identified in 91% of all cases, with strong expression of 14%, 25%, and 14% in ERM of PVR, PDR, and SRM, respectively. SEPT5 was seen in 54% of all cases; strong immunostaining was found in only one case of PVR membranes. Our finding suggests a role for members of the septin family in the development of proliferative retinal membranes.

Dynamic contour tonometry (DCT) versus Goldmann applanation tonometry (GAT) - a comparison of agreement and reproducibility.

BACKGROUND: The PASCAL dynamic contour tonometer (DCT) is a novel device designed for intraocular pressure (IOP) measurements. It is assumed to be largely independent of corneal properties. In a previous study we compared DCT with Goldmann applanation tonometry (GAT) in 100 right eyes with normal corneas. The aim of the present study is to evaluate whether differences DCT-GAT >or= 2.0 mmHg found in the previous study are reproducible and also present in the fellow eye. METHODS: Twenty-three of the 100 patients (M:F = 8:15, mean age: 36 +/- 11 SD, range 22-53 years) with a previous difference DCT-GAT >or= 2.0 mmHg were included in the present study. The minimum interval between the initial and the current examination was 3 weeks. The IOP-values of the fellow eyes in this subgroup were assessed in parallel. RESULTS: The difference DCT-GAT was 2.44 +/- 0.4 SEM mmHg in the subgroup of the 23 right eyes and 2.03 +/- 0.5 SEM mmHg for the fellow eyes, compared to 0.94 +/- 0.5 SEM mmHg in the initial sample of 100 eyes. CONCLUSIONS: In cases with higher difference between DCT-GAT, the difference is reproducible and even present in the fellow eye. We, therefore, assume that the differences are not caused by chance, but by differing biomechanical corneal properties.

Morphological changes of the retrobulbar optic nerve and its meningeal sheaths in glaucoma.

This work focuses on the possible remodeling of the intraorbital portion of the optic nerve and its meningeal sheaths in glaucoma. The bulbar segments of the orbital optic nerve portion from 25 donors with glaucoma (M:F = 8:17; mean age +/- SD 85 +/- 11 years) and 25 controls (M:F = 14:11; mean age +/- SD 81 +/- 8 years) were formalin fixed, paraffin embedded and sectioned in series. Sections were stained with PAS, Masson trichrome and CD68, and examined for the following parameters: (1) diameter of the optic nerve; (2) thickness of the pia mater; (3) distance between dura mater and pia mater; (4) occurrence and amount of meningothelial cell nests in the subarachnoid space, and (5) presence and number of corpora arenacea. The mean diameter of the optic nerve was decreased in the glaucoma group when compared to the controls (2.9 +/- 0.5 vs. 3.3 +/- 0.5 mm; p < 0.01). The thickness of the pia mater was increased in the glaucoma group (0.1 +/- 0.04 vs. 0.09 +/- 0.03 mm, p < 0.05). Presence and number of corpora arenacea did not differ between the groups. Occurrence and amount of meningo- thelial cell nests in the subarachnoid space were however significantly increased in glaucoma (p < 0.02). Whether this observation is glaucoma specific deserves further investigation.

Thermoregulatory effects of melatonin in relation to sleepiness.

Thermoregulatory processes have long been implicated in the initiation of human sleep. In this paper, we review our own studies conducted over the last decade showing a crucial role for melatonin as a mediator between the thermoregulatory and arousal system in humans. Distal heat loss, via increased skin temperature, seems to be intimately coupled with increased sleepiness and sleep induction. Exogenous melatonin administration during the day when melatonin is essentially absent mimics the endogenous thermophysiological processes occurring in the evening and induces sleepiness. Using a cold thermic challenge test, it was shown that melatonin-induced sleepiness occurs in parallel with reduction in the thermoregulatory set-point (threshold); thus, melatonin may act as a circadian modulator of the thermoregulatory set-point. In addition, an orthostatic challenge can partially block the melatonin-induced effects, suggesting an important role of the sympathetic nervous system as a link between the thermoregulatory and arousal systems. A topographical analysis of finger skin temperature with infrared thermometry revealed that the most distal parts of the fingers, i.e., fingertips, represent the important skin regions for heat loss regulation, most probably via opening the arteriovenous anastomoses, and this is clearly potentiated by melatonin. Taken together, melatonin is involved in the fine-tuning of vascular tone in selective vascular beds, as circulating melatonin levels rise and fall throughout the night. Besides the role of melatonin as "nature's soporific", it can also serve as nature's nocturnal vascular modulator.

A sick eye in a sick body? Systemic findings in patients with primary open-angle glaucoma.

Despite intense research, the pathogenesis of primary open-angle glaucoma (POAG) is still not completely understood. There is ample evidence for a pathophysiological role of elevated intraocular pressure; however, several systemic factors may influence onset and progression of the disease. Systemic peculiarities found in POAG include alterations of the cardiovascular system, autonomic nervous system, immune system, as well as endocrinological, psychological, and sleep disturbances. An association between POAG and other neurodegenerative diseases, such as Alzheimer disease and Parkinson disease, has also been described. Furthermore, the diagnosis of glaucoma can affect the patient's quality of life. By highlighting the systemic alterations found in POAG, this review attempts to bring glaucoma into a broader medical context.

Anatomic site-specific patterns of gene copy number gains in skin, mucosal, and uveal melanomas detected by fluorescence in situ hybridization.

To assess the differences between melanomas of different location and different etiology, 372 malignant melanomas were brought in a tissue microarray format. The collection included 23 acral and 118 non-acral skin melanomas, 9 mucosal melanomas, 100 uveal melanomas, and 122 melanoma metastases. Fluorescence in situ hybridization (FISH) was used to assess copy number changes of the cyclin D1 (CCND1), MDM2, c-myc (MYC), and HER2 genes. FISH analysis revealed distinct differences between melanomas from different locations. CCND1 amplifications were detected in skin melanomas from sites with chronic sun exposure (6 of 32 cases), acral melanomas (4 of 17 cases), and mucosal melanomas (one of ten cases) but not in uveal melanomas. High-level MDM2 amplifications were exclusively present in acral melanomas (2 of 19 cases). MYC copy number gains were detected in 32 of 71 uveal melanomas, five of eight mucosal melanomas, and 6 of 67 melanomas from sites with intermittent sun exposure but not in acral melanomas nor melanomas from sites with chronic sun exposure. Alterations of the MYC gene were associated with advanced tumor stage. There were no high-level HER2 amplifications. Site-specific genetic and epigenetic features may impact the response of melanomas to various anti-cancer drugs and should be considered in future studies on the molecular pathogenesis of malignant melanomas.

Expression of sex hormone receptors and cell cycle proteins in melanocytic lesions of the ocular conjunctiva.

BACKGROUND: Both dermal and ocular melanocytic nevi have been reported to undergo changes during pregnancy. This has been proposed to be related to hormonal influences; however, few studies have provided any proof. We therefore set out to evaluate the expression of sex hormone receptors and cell cycle proteins in melanocytic lesions of the ocular conjunctiva. METHODS: Formalin-fixed, paraffin-embedded material from 76 tumors--69 conjunctival nevi, 5 specimens of primary acquired melanosis (PAM), and 2 conjunctival melanomas--were included in a tissue microarray (TMA) format. The TMA sections were analyzed by immunohistochemistry with antibodies for progesterone and estrogen receptors, and cell cycle-related proteins (p16, MIB1-Ki67). RESULTS: Progesterone receptors were highly (96%) and similarly expressed in all lesions. In addition, progesterone receptor expression showed a tendency to increase with age (p=0.06). In contrast, estrogen receptor expression was completely absent in all tumors. The cell cycle regulator p16 was expressed in 97% of the lesions. The proliferation marker MIB1-Ki67 was expressed at low levels (mean+/-SD: 13+/-14%) in 79% of the lesions. No differences of expression were found between the different lesions and nevi types. The mean age of the patients was highest in conjunctival melanoma (70+/-22 years), followed by PAM (60+/-19 years) and nevi (36+/-18 SD years). The different types of nevi also showed significant age dependency (junctional 25+/-17 years, compound 34+/-17 years, dermal 49+/-15 years). CONCLUSION: Our findings reveal the expression of progesterone, but not estrogen, in melanocytic lesions of the ocular conjunctiva. In benign conjunctival lesions, p16 and MIB1-Ki67 expression was comparable to that in benign nevi of the skin.

Immunoreactivity of the septins SEPT4, SEPT5, and SEPT8 in the human eye.

We aimed to examine the distribution of SEPT4, SEPT5, and SEPT8 in the human eye. For each septin, five to six normal human eyes were examined by immunohistochemical staining of paraffin sections using polyclonal antibodies against SEPT4, SEPT5, and SEPT8 and an avidin biotin complex immunodetection system. SEPT4 immunoreactivity (IR) was detected primarily in the epithelium of cornea, lens, and nonpigmented ciliary epithelium; in the endothelium of cornea and vessels of iris and retina; and in the retinal nerve fiber layer, the outer plexiform layer, the outer segments of the photoreceptor cells, the inner limiting membrane of the optic nerve head, and optic nerve axons. SEPT5-IR was present in corneal endothelial cells, iris tissue, nonpigmented ciliary epithelium, and epithelial cells of the lens. SEPT8-IR almost paralleled that of SEPT4, except for a lower SEPT8-IR of the outer photoreceptor segments and a positive staining of the meningothelial cell nests in the subarachnoidal space of the bulbar segment of the orbital optic nerve. In conclusion, SEPT4, SEPT5, and SEPT8 are expressed in various ocular tissues, each revealing a distinct expression pattern. Both physiological and potential pathophysiological role of septins in the human eye deserve further investigation.

Angiographic findings in arteriovenous dissection (sheathotomy) for decompression of branch retinal vein occlusion.

BACKGROUND: Arteriovenous dissection (sheathotomy) is a new therapeutic option in patients with branch retinal vein occlusion (BRVO) and macular involvement. We present an angiographic follow-up of 22 patients who underwent arteriovenous dissection (AVD). METHODS: Twenty-two patients (15 women; mean age 68.7+/-8.0 years) were examined preoperatively and 6 weeks, 3 months, 6 months, and 1 year after AVD. For assessment of retinal hemodynamics, arteriovenous passage time (AVP) of the affected and unaffected branches at first (AVPe) and at maximal (AVPmax) venous filling were measured. Changes in the foveal avascular zone (FAZ) were calculated to determine foveal structural changes. Visual acuity was assessed as functional parameter. RESULTS: The early AVP (AVPe) of the affected branch increased from 4.4+/-0.8 s preoperatively to 4.9+/-0.6 s 6 weeks after surgery and decreased to 2.7+/-0.4 s 1 year after surgery (p=0.05). When compared to the unaffected control branch, AVPe was significantly increased in the affected branch preoperatively (4.5+/-0.8 s versus 1.5+/-0.2 s, p<0.01), 6 weeks (4.9+/-0.6 s versus 2.1+/-0.3 s, p<0.01), 3 months (2.7+/-0.4 s versus 1.5+/-0.2 s, p<0.01), and 6 months (3.1+/-0.4 s versus 2.2+/-0.3 s, p=0.02) after AVD. After 1 year, AVPe no longer differed between the affected and the control branch (2.7+/-0.4 s versus 2.6+/- 0.3 s). AVPmax was significantly increased in the affected branch preoperatively (11.8+/-0.8 s versus 7.7+/-1.0 s, p<0.05). The AVPmax in the affected branch with the exception of 3 months after surgery (10.2+/-1.1 s, p<0.01) was no longer elevated when compared to preoperative values. The area of the FAZ did not change significantly but showed a trend for enlargement. CONCLUSION: AVD for decompression of BRVO leads to a significant decrease of AVP and may ameliorate retinal perfusion in the affected branch.

Dynamic contour tonometry versus Goldmann applanation tonometry: a comparative study.

BACKGROUND: Various sources of error, including central corneal thickness (CCT) and structural corneal rigidity, have been proposed for Goldmann applanation tonometry (GAT). The Pascal dynamic contour tonometer (DCT) is a novel device designed for intraocular pressure (IOP) measurements assumed to be largely independent of CCT and corneal curvature. We compared DCT with GAT in eyes with normal corneas of various thickness. METHODS: We prospectively measured IOP using DCT and GAT in random order in 100 eyes of 100 subjects (M:F=46:54; mean age 42+/-19, range 23-88 years). RESULTS: Mean DCT values were about 1 mm Hg higher than GAT readings (16+/-3 vs 15+/-3 mmHg, p=0.001). Bland-Altman analysis of individual pairs of DCT and GAT measurements revealed a bias of -1.0 mmHg [95% confidence interval (CI): +/-1.2]. Neither GAT nor DCT showed a significant correlation with CCT (533+/-48, range 399-641 microm). CONCLUSIONS: In eyes with normal corneas, DCT allows suitable and reliable IOP measurements which are in good concordance with GAT. Comparison of DCT with intracameral manometry is desirable in the future.

Expression and amplification of therapeutic target genes in retinoblastoma.

PURPOSE: We set out to evaluate alterations of the therapeutic target genes KIT (CD 117), EGFR, and HER-2 in human retinoblastoma. METHODS: Ninety-five formalin-fixed, paraffin-embedded retinoblastomas were brought into a tissue microarray (TMA) format. Immunohistochemistry was performed to analyze the expression of CD117, EGFR, and HER-2. Fluorescence in situ hybridization (FISH) was utilized for detection of EGFR amplifications. Three tumors with strong CD117 positivity were sequenced for KIT exon 11 mutations. RESULTS: Detectable CD117 expression was seen in 19% of all interpretable cases. Sequence analysis of the three tumors with the strongest CD117 expression revealed no mutations. EGFR was positive in 14% of all cases. No EGFR amplification was observed by FISH, however. All tumors were negative for HER-2 expression. CONCLUSIONS: Our data suggest that selected cases of retinoblastoma may be candidates for anti-EGFR and imatinib mesylate (STI571) therapy.

Sequence analysis and high-throughput immunohistochemical profiling of KIT (CD 117) expression in uveal melanoma using tissue microarrays.

We aimed to immunohistochemically examine the expression of KIT (CD 117) in human posterior uveal melanoma and to analyze KIT-positive tumors for gene mutations. Brought into a tissue microarray (TMA) format were 101 formalin-fixed, paraffin-embedded posterior uveal melanomas. Immunohistochemistry was performed using the polyclonal anti-CD117 antibody from Dako (A4502). In ten selected KIT-positive tumors, exons 2, 8, 9, 11, 13 and 17 were sequenced. Of the 101 cases, 89 (88%) could be evaluated on the TMAs. Immunohistochemistry for CD 117 was weakly positive in 5 cases (6%), moderately positive in 10 cases (12%) and strongly positive in 57 cases (69%). No KIT mutations were detected in the analyzed exons. In conclusion, human posterior uveal melanoma frequently expresses CD117 at high levels. Although KIT mutations could not be found, it appears justified to investigate the utility of imatinib mesylate in the treatment of these patients.

Colour vision deficiencies in Alzheimer's disease.

OBJECTIVE: visual disorders are among the earliest symptoms of Alzheimer's disease. It is, however, still controversial as to whether Alzheimer's disease impairs colour vision. In this study, colour vision of Alzheimer's disease patients was tested using the Ishihara test and the PV-16 choice test. The latter test, primarily designed for children, was chosen in order to avoid problems due to cognitive decline. METHODS: 26 patients with mild to severe Alzheimer's disease (M:F=5:21; mean age: 80+/-9 years, range: 53-95 years) and 25 controls (M:F=5:20; mean age 80+/-10 years, range: 56-100 years) were rated after undergoing complete neuro-ophthalmologic examination. RESULTS: the Alzheimer's disease patients made significantly more unspecific errors in the Ishihara test (P=0.02) and in the PV-16 choice test (P=0.0008) than the controls. No relation between test performance and severity of Alzheimer's disease was found. CONCLUSIONS: Alzheimer's disease patients have an unspecific colour vision deficiency independent of the severity of the disease.

Extraocular blood flow and endothelin-1 plasma levels in patients with multiple sclerosis.

In order to evaluate whether plasma levels of the potent vasoconstrictor endothelin-1 (ET-1) are increased in patients with multiple sclerosis (MS) and whether these patients exhibit an ET-1-mediated vascular dysregulation, ET-1 plasma levels were measured in 30 patients with MS. Blood flow velocities in the ophthalmic artery, central retinal artery, central retinal vein, short lateral posterior ciliary artery, and short medial posterior ciliary artery were assessed in parallel. ET-1 plasma levels were significantly increased in MS patients when compared to sex- and age-matched healthy controls (2.0 +/- 0.4 pg/ml, range 1.1-2.8 vs. 1.5 +/- 0.2 pg/ml, range 0.9-2.0; p < 0.001). Moreover, the patients exhibited significant alterations of extraocular blood flow. The role of ET-1 in the inflammatory process remains to be clarified.

Dawn-dusk simulation light therapy of disturbed circadian rest-activity cycles in demented elderly.

We investigated whether low intensity dawn-dusk simulation (DDS), a 'naturalistic' form of light therapy designed to embed sleep in its accustomed phase, could improve the disturbed circadian rest-activity cycle, nocturnal sleep and and/or cognitive functions in dementia. A protocol of 3 weeks each of baseline, treatment and follow-up was completed by 13 patients (85yr old+/-5yr, MMSE 14+/-5; n=9 DDS versus n=4 'placebo' dim red light) who wore an activity/lux monitor throughout. There were no significant changes in clinical or cognitive status, nor modification of circadian stability or amplitude characteristics of the rest-activity cycle. However, two aspects of sleep responded to DDS but not to dim red light. The main sleep episode was 1:14h earlier during treatment (p=0.03) compared with before and after DDS. With respect to actimetry-determined sleep variables, the DDS group tended to have shortened 'sleep latency', longer 'sleep duration', more nocturnal immobility and less nocturnal activity than the dim red group (p<0.1). In parallel, nighttime light exposure tended to be reduced (p=0.07). These promising findings-after only 3 weeks of light treatment in elderly patients with advanced dementia-suggest that the circadian timing system remains functionally responsive even to low intensity DDS light. Increasing zeitgeber strength is an important strategy for improving sleep quality and timing in dementia, and DDS light therapy may provide one of the appropriate means to do so.

Unilateral fungal and mycobacterial keratitis after simultaneous laser in situ keratomileusis.

PURPOSE: To report a case of unilateral fungal and mycobacterial keratitis after simultaneous laser in situ keratomileusis (LASIK). METHODS: Case report of a 37-year-old woman who developed corneal infiltrates located at the flap-stroma interface in her left eye 3 weeks after LASIK for myopia. The infiltration progressed despite topical antibiotic therapy; therefore, the flap was lifted and irrigated with antibiotic solution. Parallel corneal scrapings were taken. The patient's condition deteriorated, prompting a lamellar keratoplasty. RESULTS: Corneal scrapings demonstrated no growth. Microbiologic cultures of the corneal specimen were reported as negative, whereas histopathologic examination disclosed fungal filaments. Two months later, the patient presented corneal infiltrates of the left eye again. Because the situation worsened despite therapy, a penetrating keratoplasty was performed. Histopathologic examination of the host cornea revealed no pathogenic species; microbiologic cultures, however, demonstrated Mycobacterium chelonae. CONCLUSION: Fungi and M. chelonae are rare and insidious causes of infectious keratitis after LASIK. Our case emphasizes the possible difficulties in diagnosing and treating a combined or subsequent infection with both species.

Increased plasma levels of 20S proteasome alpha-subunit in glaucoma patients: an observational pilot study.

PURPOSE: Several reports have shown that proteasome levels may change during pathological processes. Here we investigated whether altered gene expression of the alpha-subunit of 20S proteasomes in leukocytes of glaucoma patients at the level of mRNA, shown by us earlier, is reflected by the level of protein synthesis. METHODS: Western blot analysis was performed to determine the protein levels of the 20S proteasome alpha-subunit in leukocytes of 12 glaucoma patients (6 HTG and 6 NTG) and 6 healthy controls. RESULTS: Plasma levels of the 20S proteasome alpha-subunit showed a 3.4+/-0.47 (mean+/-SD; p<0.0001) fold increase in glaucoma patients when compared to healthy controls. In addition, normal tension glaucoma patients revealed a more pronounced alpha-subunit expression (p<0.05) when compared to patients with high tension glaucoma. CONCLUSIONS: During the pathological process of glaucoma, proteasome protein levels increase. This indicates that proteasome protein levels may be a diagnostic or eventually a prognostic marker for glaucomatous damage.

Elevated plasma endothelin-1 levels and vascular dysregulation in patients with rheumatoid arthritis.

BACKGROUND: Contradictory results on plasma endothelin-1 (ET-1) levels in patients with rheumatoid arthritis have been reported in previous studies. We therefore evaluated whether plasma ET-1 levels in patients with rheumatoid arthritis differ from those of normal controls. Since systemically increased levels of ET-1 are known to occur in tandem with primary or secondary vascular dysregulation, we also measured peripheral blood flow by means of nailfold capillaroscopy combined with a cold provocation test. MATERIAL/METHODS: We measured plasma levels of ET-1 in twelve patients with different stages of rheumatoid arthritis by means of a specific radioimmunoassay, and compared ET-1 values to those of healthy controls. Capillary blood flow and the frequency of cold-induced vasospasm were studied in parallel, using nailfold capillaroscopy combined with a cold provocation test. RESULTS: Plasma ET-1 levels were significantly increased in patients with rheumatoid arthritis (p = 0.01) when compared to controls (2.38+/-0.95 pg/ml vs. 1.53+/-0.38 pg/ml). Capillary blood flow was reduced when compared to our own normal values, and a cold-induced blood standstill was seen in 58% of the patients. CONCLUSIONS: Patients with rheumatoid arthritis exhibit significantly elevated levels of ET-1, which may be associated with the symptoms of vascular dysregulation observed in nailfold capillaroscopy. Even though the clinical conclusions should be drawn from this study with caution, additional therapy with calcium channel blockers or, possibly in the future, with ET-1 receptor blockers, may be beneficial in patients with rheumatoid arthritis.

Effect of melatonin on vascular responses of porcine ciliary arteries.

PURPOSE: To investigate the effect of melatonin on isolated porcine ciliary arteries. METHODS: Isolated porcine ciliary arteries were suspended in myograph chambers filled with modified Krebs-Ringer solution (37 degrees C; 95% O2/5% CO2) for isometric tension recording. RESULTS: In quiescent porcine ciliary arteries with endothelium, melatonin (10(-11)--10(-5) M) evoked no change in vascular tone. The highest concentration of melatonin (10(-4 ) M) evoked a small but significant contraction. In vessels precontracted with U-46619 (10(-7) M), increasing concentrations of melatonin (10(-11)--10(-5) M) did not evoke a response. In precontracted arteries with endothelium, contractile response of vascular smooth muscle to increasing concentrations of serotonin (10(-10)--10(-5) M) and noradrenaline (10(-10)--10(-5) M) was reduced after preincubation with melatonin (10(-4) M). Melatonin (10(-4) M) did not alter the response to endothelin-1 (10(-10)--10( -7) M) and U-46619 (10(-10)--10(-6 ) M) in precontracted arteries with endothelium. CONCLUSION: These findings demonstrate that melatonin attenuates the effect of serotonin and noradrenaline and is itself a mild vasoconstrictor in porcine ciliary arteries. The role of melatonin in human ocular circulation remains to be established.