Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Retinitis”

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 289 records · Page 16Linked to original sources

Carbonic anhydrase inhibition increases retinal oxygen tension and dilates retinal vessels.

BACKGROUND: Carbonic anhydrase inhibitors (CAIs) increase blood flow in the brain and probably also in the optic nerve and retina. Additionally they elevate the oxygen tension in the optic nerve in the pig. We propose that they also raise the oxygen tension in the retina. We studied the oxygen tension in the pig retina and optic nerve before and after dorzolamide injection. Also the retinal vessel diameters during carbonic anhydrase inhibition were studied. METHODS: A polarographic oxygen electrode was placed transvitreally immediately over the retina or the optic disc in anaesthetised pigs. The oxygen tension was recorded continually and 500 mg dorzolamide was injected intravenously. Retinal vessel diameters were analysed from monochromatic fundus photographs taken before and after injection of dorzolamide. RESULTS: Baseline retinal oxygen tension (RPO2) was 3.34+/-0.50 kPa (mean +/- SD, n=6) and baseline optic nerve oxygen tension (ONPO2) was 3.63+/-1.00 kPa. RPO2 was increased by 0.36+/-0.11 kPa (n=6, P=0.025) and ONPO2 by 0.73+/-0.34 kPa (n=6, P=0.003) 30 min after dorzolamide administration. The retinal arterioles was significantly dilated by 13+/-7% (n=5, P=0.016) and the retinal venules by 12+/-8% (n=5, P=0.030) 30 min after injection of dorzolamide. CONCLUSION: Retinal and optic nerve oxygen tension increased with systemic administration of dorzolamide. The retinal vessels dilated, probably causing increased blood flow inducing the observed increase in RPO2. The increased oxygenation of retina by CAI may offer therapeutic possibilities in ischaemic diseases of the retina and optic nerve.

Animals↗

The age-dependent decrease in the myogenic response of retinal arterioles as studied with the Retinal Vessel Analyzer.

PURPOSE: To study the age-dependent change in myogenic response of retinal arterioles. METHODS: Fifty-one healthy volunteers with at least ten persons in each of the five age decades (I-V) between 20 and 69 years were subjected to diameter measurement of retinal arterioles using the Retinal Vessel Analyzer (RVA) during rest and during an increase in the systemic blood pressure when lifting hand weights. The transmural pressure in the retinal arterioles during the procedures was estimated from the blood pressure and the intraocular pressure and was compared to the accompanying diameter response. RESULTS: The retinal arteriolar diameter showed a significant decrease as a function of increasing weight for the two younger age groups below the age of 40 years (P=0.007, group I, and P=0.049, group II), compatible with perfect autoregulation, whereas no such change was observed in persons above this age (P=0.41, 0.053, 0.29 for groups III-V, respectively). CONCLUSION: Studies on autoregulation in retinal disease should consider the normal age-related decrease in diameter response of retinal arterioles when the blood pressure is changed.

Adult↗

Retinal vasculitis and vitreous hemorrhage associated with mixed connective tissue disease: retinal vasculitis in MCTD.

BACKGROUND: Retinal vasculitis associated with mixed connective tissue disease (MCTD) has rarely been reported in the literature. We describe a rare case of a patient with serious retinal vasculopathy and vitreous hemorrhages associated with MCTD. CASE: A 53-year-old woman with MCTD who has had recurrent retinal vasculitis and vitreous hemorrhage in the right eye since 2000 presented with blurred vision in the right eye in April 2003. The best-corrected visual acuity was counting finger in the right eye. The patient was clinically diagnosed as having retinal and vitreous hemorrhages and retinal infarction. Prednisolone was administered orally in a daily dose of 20 mg. RESULTS: The retinal and vitreous hemorrhage improved in 7 days. The best-corrected visual acuity improved to more than 20/20 on prednisolone alone. CONCLUSION: MCTD can be associated with retinal vasculitis and vitreous hemorrhage which in our case responded well to systematic low doses of corticosteroid therapy.

Adult↗

Preliminary report: indications of improved visual function after retinal sheet transplantation in retinitis pigmentosa patients.

PURPOSE: To report indications of new visual function after retinal transplantation in two blind patients with retinitis pigmentosa. METHODS: Intact sheets of fetal retina (15 and 17 weeks gestational age) were transplanted subretinally (between the neurosensory retina and the retinal pigment epithelium) near the fovea in the left eye of a 23-year-old white man (Patient A) and in the left eye of a 72-year-old white woman (Patient B), both with autosomal-recessive retinitis pigmentosa. RESULTS: Postoperatively, at 6 and 5 months, respectively, both patients reported new visual sensation in the visual field corresponding to the transplant. In both patients, the visual sensation continued to be present after transplantation, at 12 and 8 months, respectively. In Patient A, a transient multifocal electroretinography (mfERG) response was observed in the transplant area 4 months postoperatively but was not detectable in Patient A at 6.0 and 9.5 months post-retinal transplantation. In Patient B, no positive mfERG responses were seen up to 5 months postoperatively. No rejection (presenting as cystoid macular edema, macular pucker, and extensive intraretinal edema with disrupted retinal pigment epithelium) to the transplanted tissue was seen up to 13 months in Patient A and 9 months in Patient B by fluorescein angiography. CONCLUSION: Transplantation of intact sheets of fetal human retina in two patients with retinitis pigmentosa was not associated with evidence of transplant rejection. Subjective improvement and an indication of objective improvement 4 months postoperatively were seen in Patient A, and subjective improvement only was seen in Patient B.

Adult↗

Cilostazol, a selective cAMP phosphodiesterase inhibitor, dilates retinal arterioles and increases retinal and choroidal blood flow in rats.

The effects of cilostazol, a selective cyclic AMP (cAMP) phosphodiesterase inhibitor, on retinal and choroidal blood flow and retinal arteriole diameter were examined in anesthetized rats. The retinal and choroidal blood flow was measured using laser Doppler flowmetry, and the diameter of the retinal arterioles was measured using digital video microscopy. Cilostazol was administered by two routes; systemically via the intravenous route, and directly into the retinal vessels via the intra-arterial route. When administered intravenously, 1 mg/kg of cilostazol produced a biphasic blood flow response, composed of an initial decrease which was dependent on a depressor response of mean arterial pressure, and a subsequent slight but significant increase which was independent of changes in mean arterial pressure. When administered intra-arterially over a 2-min period, 40-55 and 400-440 microg of cilostazol both produced an increase in the blood flow in a dose-dependent manner, while a depressor effect was observed only at the dose of 400-440 microg. The diameter of the retinal arterioles was increased after the intra-arterial injection of cilostazol (400 microg). It is concluded that intra-arterially administered cilostazol induces vasodilation of the retinal arterioles of rats, which results in an increase in blood supply to the retina, independent of changes in mean arterial pressure.

3',5'-Cyclic-AMP Phosphodiesterases↗

The Artificial Synapse Chip: a flexible retinal interface based on directed retinal cell growth and neurotransmitter stimulation.

The Artificial Synapse Chip is an evolving design for a flexible retinal interface that aims to improve visual resolution of an electronic retinal prosthesis by addressing cells individually and mimicking the physiological stimulation achieved in synaptic transmission. We describe three novel approaches employed in the development of the Artificial Synapse Chip: (i) micropatterned substrates to direct retinal cell neurite growth to individual stimulation sites; (ii) a prototype retinal interface based on localized neurotransmitter delivery; and (iii) the use of soft materials to fabricate these devices. By patterning the growth of cells to individual stimulation sites, we can improve the selectivity of stimulation and decrease the associated power requirements. Moreover, we have microfabricated a neurotransmitter delivery system based on a 5- micro m aperture in a 500-nm-thick silicon nitride membrane overlying a microfluidic channel. This device can release neurotransmitter volumes as small as 2 pL, demonstrating the possibility of chemical-based prostheses. Finally, we have fabricated and implanted an equivalent device using soft flexible materials that conform to the retinal tissue more effectively. As many of the current retinal prosthesis devices use hard materials and electrical excitation at a lower resolution, our approach may provide more physiologic retinal stimulation.

Animals↗

[Retinal vessel reaction to 100% O2-breathing--functional imaging using the retinal vessel analyzer with 10 volunteers].

BACKGROUND: Retinal vessel diameter assessment is complicated by various components among them dynamic changes due to vasomotoric effects. Measurement of these diameters was usually obtained from fundus photographs. Functional diameter changes induced by external stimuli were difficult to evaluate because of their dynamic nature. The Retinal Vessel Analyzer (RVA) allows continuous on-line measurement of those dynamic changes. Whether functional changes due to 100% O2 breathing can be assessed by RVA is investigated in this study. MATERIALS AND METHODS: Continuous on-line registration of retinal arterial and venous branch vessels was obtained in 10 healthy volunteers. A baseline was taken during the first minute. Then for 5 minutes 100% O2 was delivered by mask. Further recording ensued for 4 minutes, while breathing room air. Vessel diameter change in percent to baseline was calculated for each individual and for a mean of the group. RESULTS: Each individual demonstrated vasoconstriction. The mean diameter reduction for the group was 6.5% for arteries and 15% for veins. CONCLUSIONS: RVA allows assessment of functional retinal branch vessel reactions. Retinal branch vessels diameters are denominators for capillary perfusion. RVA might be able to demonstrate an individual vessel's regulation potential by purposeful stimulation to constrict and dilate. This property could be helpful in understanding pathophysiologic processes as well as improving diagnosis and therapeutic effects in diseases influencing ocular perfusion such as diabetes, retinal vessel occlusion or even glaucoma. Further evaluation of effects of systemic diseases might be an additional application of functional retinal vessel diameter assessment by RVA.

Adult↗

Retinal photocoagulation does not influence intraocular levels of IGF-I, IGF-II and IGF-BP3 in proliferative diabetic retinopathy-evidence for combined treatment of PDR with somatostatin analogues and retinal photocoagulation?

Retinal photocoagulation reduces the incidence of severe visual loss in proliferative diabetic retinopathy (PDR). Reduced levels of VEGF/VPF might result in an improved function of the blood-retina barrier and cause a decrease of blood derived intraocular growth factors such as IGF-I. This study investigates whether retinal photocoagulation is able to normalize the concentrations of IGF-I, IGF-II and IGF-BP3 in the vitreous humor of patients undergoing vitrectomy. Levels of IGFs and the permeability marker, albumin, were measured in serum and vitreous of 52 patients. Three groups were compared: controls without proliferating eye disease (n = 19) and patients with PDR with (PDR+; n = 25) and without (PDR-; n = 8) previous retinal photocoagulation. IGF-I, IGF-II, IGF-BP3 and albumin were determined by immunological methods and were confirmed to be increased in patients with PDR compared to controls. Retinal photocoagulation influenced neither the intraocular concentration of the permeability marker albumin (PDR+: 253.2 +/- 46 mg/dl; PDR-: 256.4 +/- 66.5 mg/dl) nor the levels of IGFs (PDR+: IGF-I: 1.2 +/- 0.1 ng/ml; p = 0.38; IGF-II: 34.8 +/- 2.2 ng/ml; p = 0.1; IGF-BP3: 75.7 +/- 9.7 ng/ml; p = 0.27; PDR-: IGF-I: 1.1 +/- 0.2ng/ml; IGF-II: 29.3 +/- 5.2 ng/ml; IGF-BP3: 61.5 +/- 18.3 ng/ml). Systemic levels of albumin and IGFs were not changed significantly by retinal photocoagulation. These results demonstrate that previous retinal photocoagulation in patients undergoing vitrectomy does not functionally reestablish the blood-retina barrier despite decreases in VEGF/VPF. The lack of influence on intraocular concentrations of the serum-derived growth factors, IGF-I, IGF-II and IGF-BP3, might in part explain the failure of previous photocoagulation in the investigated patients. These results suggest that a combined treatment with retinal photocoagulation and growth hormone-lowering drugs, such as somatostatin analogues, could be a useful treatment, which may prevent further loss of visual acuity in patients with PDR.

Adult↗

Isolation of canine retinal arrestin cDNA and exclusion of three candidate genes for Swedish Briard retinal dystrophy.

PURPOSE: Mutations of genes encoding various retina-specific proteins are known to cause a wide spectrum of inherited retinal dystrophies in different species. In the canine, several types of genetic retinal dystrophies have been described affecting primarily the photoreceptors and/or the retinal pigment epithelium. We are performing a systematic analysis of canine candidate genes for such diseases to identify the one mutated in the retinal dystrophy in Swedish Briard dogs. METHODS: We isolated and characterised the full length cDNA of canine retinal arrestin by the method of rapid amplification of cDNA ends (RACE). RESULTS: The full length cDNA isolated by us is 1,575 base pairs (bp) long and contains a 1,218 bp-long open reading frame. CONCLUSIONS: The homology of the canine arrestin protein is highest with the human analogue (88.9%) and lowest with mouse arrestin (85.3%). The most obvious sequence differences among the different arrestins are in the extreme carboxyl terminus. PCR-SSCP (single strand conformation polymorphism) analysis and direct sequencing of retinal cDNA didn't provide any evidence that mutations in the canine arrestin gene are responsible for the retinal dystrophy seen in the Swedish strain of Briard dogs. Similar data were obtained for the genes encoding rhodopsin and the beta-subunit of photoreceptor-specific phosphodiesterase by segregation analysis.

Amino Acid Sequence↗

Analysis of retinal findings of acute retinal necrosis using optical coherence tomography.

PURPOSE: To analyze the retinal findings in patients with ARN, optical coherence tomography (OCT) was performed. METHODS: Seven patients (7 eyes) with ARN were studied using OCT. RESULTS: OCT images depicted highly reflective areas in the inner layers of the retina in all seven cases, corresponding with the yellowish-white lesions of the retina in the acute phase. Disorganization of the retinal structure was also observed in these retinal lesions, especially in cases with severe inflammation. Subretinal changes including retinal exudate and/or fluid were observed in only one case. After regression of the yellowish-white lesions in the retina, a significant reduction in retinal thickness was observed on OCT. CONCLUSIONS: OCT permits the detection of full-thickness retinal necrosis in the acute phase and complete absence of retinal structure in the resolution phase, corresponding with the yellowish-white lesions seen in patients with ARN.

Adult↗

Interferon-beta and adhesion molecules (E-selectin and s-intracellular adhesion molecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling.

Retinal vasculitis is a major component of ocular inflammation that plays a role in retinal tissue damage in patients with idiopathic uveitis and Behçet's disease. Here we show that type 1 interferons (IFN alpha/beta) were not detected in sera from normal individuals but were identified in up to 46% of the sera from retinal vasculitis patients. The predominant form of IFN observed was IFN-beta, which was detected in 39% of Behçet's disease patients and 47% of idiopathic uveitis patients. Seven patients whose sera contained IFN-beta were monitored prospectively. IFN-beta was shown to be present for 6-12 months in all seven of the sera samples tested. Furthermore, the adhesion molecule profile identified in this study was strikingly different when Behçet's and uveitis patient sera were compared to sera from normal controls. Sera from Behçet's disease patients contained significantly elevated levels of the soluble adhesion molecules, sE-selectin and s-intracellular adhesion molecule-1 (sICAM-1), whereas sera from patients with idiopathic uveitis contained significantly increased sE-selectin. In vitro studies evaluating the cell source of these cytokines revealed that polyriboinosinic polyribocytidylic acid (poly I:C) activated retinal vascular endothelial cells produce sE-selectin, sICAM-1 and IFN-beta. Production of these molecules was inhibited by pretreatment with anti-Toll-like receptor 3 (TLR-3) antibody. In conclusion, IFN-beta, sE-selectin and sICAM-1 are elevated in patients with retinal vasculitis and are induced in retinal vascular endothelial cells in vitro by activating the innate immune system through TLR-3. Further analysis of innate immune signalling may prove to be a novel target for future studies on pathogenic mechanisms and therapeutic approaches in retinal vasculitis.

Acute Disease↗

Sealing of retinal breaks with metal tacks. Evaluation of a new procedure in retinal re-attachment surgery.

Metal retinal tacks were used in 18 patients with complicated retinal detachments, such as giant tears (3 cases), severe proliferative vitreoretinopathy (PVR) (7 eyes) and diabetic traction and rhegmatogenous detachment (8 cases). All eyes had undergone vitreous microsurgery, including excision or segmentation of epiretinal membranes, fluid-air (SF6) or silicone oil exchange. Retinal breaks and the cut edges of retinotomies and retinectomies were successfully sealed by metal tacks. Retinal re-attachment was achieved in 9 cases and partial re-attachment in another 5 eyes (follow-up 3-6 months). Retinal tears in diabetic macular detachment associated with extensive epiretinal fibrovascular membranes were also successfully sealed despite persisting traction. Our first experience indicates that the closing of retinal breaks with metal tacks is a major step forward in retinal re-attachment surgery.

Adolescent↗

Molecular and cellular reactions of retinal ganglion cells and retinal glial cells under centrifugal force loading.

PURPOSE: To investigate changes in retinal ganglion cell (RGC) survival and morphology, retinal glial cell effects on RGC survival, and changes in mRNA expression during centrifugal force loading using a newly developed device. METHODS: Changes in RGC survival and morphology were examined when isolated RGCs from 2-day-old rats were loaded with centrifugal force equivalent to 16, 28, or 33 mm Hg. The effects of cocultured retinal glial cells on RGC survival were studied in the presence of centrifugal force equivalent to 16 and 28 mm Hg for 48 hours. The microarray method and real-time polymerase chain reaction confirmed changes in mRNA expression when RGCs and retinal glial cells were loaded with centrifugal force equivalent to 28 mm Hg for 24 hours. RESULTS: The survival of isolated RGCs and the number of neurites were significantly decreased by centrifugal force loading. Conversely, there was no significant change in the survival of isolated retinal glial cells. The survival of cocultured RGCs was significantly better than that of isolated RGCs. In contrast to the numerous changes in the mRNA expression of retinal glial cells subjected to centrifugal force loading, there was no significant change in the mRNA expression of RGCs. CONCLUSIONS: The developed device may have potential for use as an in vitro model of RGC damage. The response to centrifugal force loading varies according to cell type, and the marked changes in the mRNA expression of retinal glial cells may be involved in the improvement of RGC survival.

Animals↗

Retinal thickness and subnormal retinal oxygenation response in experimental diabetic retinopathy.

PURPOSE: To test the hypothesis that subnormal retinal oxygenation response (DeltaPo2) found at 3 months of experimental diabetes is associated with cellular swelling and increased retinal thickness. METHODS: Two groups of animals were studied: control rats injected intraperitoneally with either 15% body weight of saline or distilled water (cellular swelling model) or with intravitreal N-methyl-D-aspartate (NMDA) and 3-month-old diabetic and age-matched control rats. Intraocular pressure and retinal thickness was assessed using an applanation tonometer or high-resolution MRI (23.4 microm2 in-plane). In separate studies, functional MRI was used to measure blood-retinal barrier (BRB) integrity after Gd-DTPA injection intravenously and retinal DeltaPo2 during carbogen provocation. RESULTS: Inner and total retinal thickness were lower (P < 0.05) after NMDA injection, not different (P > 0.05) between control, before and after saline injection and before distilled water injection, and supernormal (P < 0.05) after distilled water injection. In diabetic rats, thickness was normal (P > 0.05) at most distances from the optic nerve but was subnormal (P < 0.05) in superior retina (0.5 mm from the optic nerve). Intraocular pressure was not different (P > 0.05) between groups. BRB was intact (P > 0.05) after saline and distilled water injection. DeltaPo2 was normal (P > 0.05) after saline injection and over inferior hemiretina of the diabetic group but was subnormal (P < 0.05) after distilled water injection and over superior hemiretina of diabetic rats. CONCLUSIONS: The lack of increased thickness in 3-month-old diabetic rats in vivo raises the possibility that intracellular swelling is unlikely to underlie subnormal DeltaPo2 in experimental diabetes. In diabetic rats, the spatial disconnect between subnormal DeltaPo2 pansuperiorly and retinal thinning only superiorly to the optic nerve suggests that neurovascular coupling is perturbed.

Animals↗

4-(N,N-dipropylamino)benzaldehyde inhibits the oxidation of all-trans retinal to all-trans retinoic acid by ALDH1A1, but not the differentiation of HL-60 promyelocytic leukemia cells exposed to all-trans retinal.

BACKGROUND: The signal transduction pathways mediated by retinoic acid play a critical role in the regulation of cell growth and differentiation during embryogenesis and hematopoiesis as well as in a variety of tumor cell lines in culture. Following the reports that two members of the superfamily of aldehyde dehydrogenase (ALDH) enzymes, ALDH1A1 and ALDH1A2, were capable of catalyzing the oxidation of all-trans retinal to all-trans retinoic acid with submicromolar Km values, we initiated an investigation of the ability of 4-(N,N-dipropylamino)benzaldehyde (DPAB) to inhibit the oxidation of retinal by purified mouse and human ALDH1A1. RESULTS: Our results show that DPAB potently inhibits retinal oxidation, with IC50 values of 0.11 and 0.13 microM for purified mouse and human ALDH1A1, respectively. Since the HL-60 human myeloid leukemic cell line has been used extensively to study the retinoic acid induced differentiation of HL-60 cells to granulocytes, and ALDH1A1 activity had previously been reported in HL-60 cells, we investigated the ability of DPAB to block differentiation of HL-60 promyelocytic leukemia cells exposed to retinal in culture. In HL-60 cells coincubated with 1 microM retinal and 50 microM DPAB for 144 hours, cell differentiation was inhibited only 30%. Furthermore, the NAD-dependent oxidation of propanal or retinal was less than 0.05 nmoles NADH formed/min-10(7) cells in spectrophotometric assays using HL-60 cell extracts. CONCLUSION: Although ALDH1A1 may be the major catalytic activity for retinal oxidation in some retinoid-dependent mouse and Xenopus embryonic tissues and in adult human and mouse hematopoietic stem cells, another catalytic activity appears to synthesize the retinoic acid ligand necessary to stimulate the differentiation of HL-60 cells to end stage granulocytes.

Aldehyde Dehydrogenase↗

Glycosaminoglycan degradation by cultured retinal pigment epithelium from patients with retinitis pigmentosa.

Patients with certain systemic deficiencies in the degradation of glycosaminoglycans (GAGs) often suffer from a retinal degeneration similar to that seen in retinitis pigmentosa. This applies to mucopolysaccharidosis (MPS) types I, II, and III, but not to type VI. The retinal pigment epithelium (RPE) is thought to contribute significantly to the synthesis and degradation of proteoglycans in the interphotoreceptor matrix. This raises the possibility that a defect in the synthesis or degradation of GAGs by the RPE may be related to some forms of retinal degeneration. In the present work, RPE from normal and RP donors was investigated for the capacity to correct deficiencies in GAG degradation by cultured skin fibroblasts from patients with different forms of MPS. A cross-correction technique was used in which abnormal increases in the incorporation of 35S-sulfate into GAGs by MPS fibroblasts was measured in the absence or presence of RPE cultures. RPE from normal donors corrected the defects in GAG degradation of fibroblasts from patients with MPS I, II, and III, but not MPS VI. The RPE from four donors with retinitis pigmentosa (one autosomal dominant, one sex-linked, and two isolated cases) and one donor with an unclassified isolated retinal degeneration demonstrated the same capacities to correct the MPS deficiencies as did normal RPE. Therefore, although retinitis pigmentosa is a heterogeneous disorder with several possible etiologies, no evidence was found in these five patients for a defect in GAG degradation that resembles the deficiencies of MPS patients.

Adult↗

[Retinal detachments and retinal surgery].

The incidence of retinal detachment is approximately 1:10,000. Most retinal detachments occur between the ages of 50 and 65 years. A rhegmatogenous retinal detachment starts with a tear in the peripheral retina. Through this retinal tear liquefied vitreous may enter the subretinal space, resulting in a retinal detachment with progressive visual loss. In 50% prodromal light flashes are observed. Laser coagulation around a tear without subretinal fluid can make surgical intervention unnecessary in approximately 96% of cases. When subretinal fluid is present, conventional scleral buckling surgery is successful in 80-90% of the cases. In more complex retinal detachments or in re-detachment cases, a trans pars plana vitrectomy is indicated. Anatomical success can be achieved in approximately 96% of cases, sometimes after several operations. Functional success depends on preoperative pathology and duration of the detachment. Eyes with retinal detachment of the macula and with larger and complex defects have poorer visual prognosis.

Aged↗

Excess of serotonin (5-HT) alters the segregation of ispilateral and contralateral retinal projections in monoamine oxidase A knock-out mice: possible role of 5-HT uptake in retinal ganglion cells during development.

Retinal ganglion cell (RGCs) project to the ipsilateral and contralateral sides of the brain in the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC). Projections from both eyes are initially intermingled until postnatal day 3 (P3) but segregate into eye-specific layers by P8. We report that this segregation does not occur in monoamine oxidase A knock-out mice (MAOA-KO) that have elevated brain levels of serotonin (5-HT) and noradrenaline. The abnormal development of retinal projections can be reversed by inhibiting 5-HT synthesis from P0 to P15. We found that in MAOA-KO mice, 5-HT accumulates in a subpopulation of RGCs and axons during embryonic and early postnatal development. The RGCs do not synthesize 5-HT but reuptake the amine from the extracellular space. In both MAOA-KO and normal mice, high-affinity uptake of 5-HT and serotonin transporter (SERT) immunoreactivity are observed in retinal axons from the optic cup to retinal terminal fields in the SC and dLGN. In the dLGN, transient SERT labeling corresponds predominantly to the ipsilateral retinal projection fields. We show that, in addition to SERT, developing RGCs also transiently express the vesicular monoamine transporter gene VMAT2: thus, retinal axons could store 5-HT in synaptic vesicles and possibly use it as a borrowed neurotransmitter. Finally we show that the 5-HT-1B receptor gene is expressed by RGCs throughout the retina from E15 until adult life. Activation of this receptor is known, from previous studies, to reduce retinotectal activity; thus 5-HT in excess could inhibit activity-dependent segregation mechanisms. A hypothesis is proposed whereby, during normal development, localized SERT expression could confer specific neurotransmission properties on a subset of RGCs and could be important in the fine-tuning of retinal projections.

Animals↗