Bacterial distribution on the ocular surface of patients with primary Sjögren's syndrome.

Many studies have shown that gut microbial dysbiosis is a major factor in the etiology of autoimmune diseases but none have suggested that the ocular surface (OS) microbiome is associated with Sjögren's syndrome (SS). In this prospective study, we analyzed bacterial distribution on the OS in patients with primary SS. Among the 120 subjects included in this study, 48 patients (group A) had primary SS, whereas 72 subjects (group B) had dry eye symptoms that were unrelated to SS. We evaluated clinical dry eye parameters such as the OS disease index, ocular staining score (OSS), Schirmer's I test, and tear break-up time (TBUT). Conjunctival swabs were used to analyze the microbial communities from the two groups. Bacterial 16S rRNA genes were sequenced using the Illumina MiSeq platform, and the data were analyzed using the QIIME 1.9.1 program. The Shannon index was significantly lower in group A than in group B microbiota (p < 0.05). An analysis of similarity using the Bray-Curtis distance method found no difference in beta-diversity between the two groups (p > 0.05). In group A, Actinobacteria at the phylum level and Corynebacteria at the genus level exhibited low abundance than group B, but the differences were not statistically significant (p > 0.05). SS apparently decreases the diversity of the OS microbial community. These observations may be related to the pathophysiology of SS and should be investigated in future studies.

Therapeutic Efficacy of Autologous Platelet Concentrate Injection on Macular Holes with High Myopia, Large Macular Holes, or Recurrent Macular Holes: A Multicenter Randomized Controlled Trial.

We aimed to evaluate the anatomical and functional outcomes of pars-plana vitrectomy (PPV) with or without autologous platelet concentrate (APC) injection in patients with recurrent macular holes (MHs), large MHs, or MHs with high myopia. This multicenter, prospective, interventional randomized controlled trial was conducted from March 2017 to April 2020. Participants were randomly allocated to a PPV group or a PPV+APC group. All participants underwent standard 25-gauge PPV, and eyes in the PPV+APC group underwent PPV with intravitreal APC injection before air-gas exchange. A total of 117 patients were enrolled (PPV group: n = 59, PPV+APC group: n = 58). Hole closure was achieved in 47 participants (79.7%) in the PPV group and 52 participants (89.7%) in the PPV+APC group. There were no between-group differences in the anatomical closure rate or functional outcomes including best-corrected visual acuity, metamorphopsia, pattern-reversal visual evoked potential, or Visual Function Questionnaire-25 score. The use of APC injection does not improve the anatomical and functional outcomes of surgery for large MHs, recurrent MHs, or MHs with high myopia. The adjunctive use of APC can be considered in selected cases because it is not inferior to conventional MH surgery, is relatively simple to perform, and is not affected by the surgeon's skill.

Machine learning prediction of pathologic myopia using tomographic elevation of the posterior sclera.

Qualitative analysis of fundus photographs enables straightforward pattern recognition of advanced pathologic myopia. However, it has limitations in defining the classification of the degree or extent of early disease, such that it may be biased by subjective interpretation. In this study, we used the fovea, optic disc, and deepest point of the eye (DPE) as the three major markers (i.e., key indicators) of the posterior globe to quantify the relative tomographic elevation of the posterior sclera (TEPS). Using this quantitative index from eyes of 860 myopic patients, support vector machine based machine learning classifier predicted pathologic myopia an AUROC of 0.828, with 77.5% sensitivity and 88.07% specificity. Axial length and choroidal thickness, the existing quantitative indicator of pathologic myopia only reached an AUROC of 0.758, with 75.0% sensitivity and 76.61% specificity. When all six indices were applied (four TEPS, AxL, and SCT), the discriminative ability of the SVM model was excellent, demonstrating an AUROC of 0.868, with 80.0% sensitivity and 93.58% specificity. Our model provides an accurate modality for identification of patients with pathologic myopia and may help prioritize these patients for further treatment.

The Shape of Posterior Sclera as a Biometric Signature in Open-angle Glaucoma: An Intereye Comparison Study.

PURPOSE: To characterize intereye differences in posterior segment parameters and determine their significance in open-angle glaucoma patients with unilateral damage. METHODS: Both eyes from 65 subjects without any nerve damage and 43 patients undergoing treatment for unilateral open-angle glaucoma were included in this study. A 12.0×9.0×2.6 mm volume of the posterior segment in each eye was scanned with swept-source optical coherence tomography. Coronally reconstructed optical coherence tomography images were analyzed to determine the deepest point of the eye (DPE), which we then calculated the distance (Disc-DPE distance), depth (Disc-DPE depth), angle (Disc-DPE angle) from the optic disc center to the DPE. Posterior pole shape was analyzed measuring the posterior pole-cross-sectional area, posterior pole-horizontal width (PP-HW), and posterior pole-vertical width) of the posterior pole. These measurements and their intereye absolute difference (IAD; absolute difference in measurements between the right and left eyes) values were compared between the healthy and unilateral glaucomatous patients. RESULTS: The posterior sclera measurements, including the Disc-DPE distance, Disc-DPE depth, and posterior pole-cross-sectional area, were significantly different between the unilateral glaucoma eyes and contralateral healthy eyes (P=0.043, P=0.035, and P=0.049, respectively). By contrast, none of the intereye differences in optic nerve head parameters were significant in the unilateral glaucoma patients. In comparison with the IAD values, the baseline intraocular pressure and PP-HW of the posterior segment showed significant differences between the healthy and the unilateral glaucoma patients (P=0.019 and P=0.036, respectively). A multivariate analysis showed that a larger baseline intraocular pressure IAD [odds ratio (OR), 1.381; P=0.009)] and larger PP-HW IAD (OR, 1.324; P=0.032) were significantly associated with the presence of glaucoma. CONCLUSIONS: Compared with the fellow healthy eyes, glaucomatous eyes had larger and more steeply curved posterior poles, which represent a structural variation of the posterior sclera that might be associated with glaucomatous optic neuropathy.

Genetic risk score combining six genetic variants associated with the cellular NRF2 expression levels correlates with Type 2 diabetes in the human population.

BACKGROUND: Type 2 diabetes (T2D) is known as an inflammatory disease. NRF2 (Nuclear Factor Erythroid 2 Like2) encodes a transcription factor that binds to antioxidant response elements (AREs) and regulates the expression of genes involved in many antioxidant responses. OBJECTIVE: This study aimed to gain insight into individual anti-inflammatory activity to prevent T2D development in humans. METHODS: We performed a genome-wide association study (GWAS) to identify genetic variants influencing NRF2 expression in LCLs (lymphoblastoid cell lines) generated from 74 different individuals. Association analyses between T2D or its related traits and genetic risk score (GRS) calculated by combining genetic variants detected from GWAS for cellular NRF2 expression were performed using data from 8715 subjects. The T2D prediction model using GRS was evaluated by measuring the area under the curve (AUC) of the receiver operating characteristics (ROC) curve. RESULTS: Our GWAS identified six genetic variants (SNP) showing suggestive evidence of associations with cellular NRF2 expression (P < 10- 6). Logistic regression analysis demonstrated that GRS was associated with an increased risk of T2D (P value = 0.003, OR = 1.13). In addition, linear regression analyses showed positive associations between GRS and fasting glucose (P value = 0.028, ß = 0.62), 2-h glucose (P value = 0.0004, ß = 1.13) and HbA1C (P value = 0.033, ß = 0.03). In the T2D prediction model using GRS, the AUC of the ROC curve was 0.69. CONCLUSION: This study highlights genetic variants associated with cellular NRF2 expression and suggests that the GRS of NRF2 expression-associated variants is likely to be a useful indicator of T2D development in the human population.

Distribution and Diversity of Ocular Microbial Communities in Diabetic Patients Compared with Healthy Subjects.

PURPOSE: The aim of this study was to identify differences in the major (core vs. variable) microbial genera of human subjects with and without diabetes. METHODS: Bacterial 16S rRNA genes obtained from conjunctival swabs of 19 healthy subjects and 30 diabetic patients were sequenced using the Illumina MiSeq platform, and the sequencing data were analyzed using QIIME 1.9.1. To elucidate the microbial diversity in the ocular surface (OS), test programs from various bioinformatics domains were used. RESULTS: Diversity index and rarefaction analysis showed that the microbial community of the diabetic patients was more diverse than that of the healthy subjects. Proteobacteria, Firmicutes, Actinobacteria, Cyanobacteria and Bacteroidetes were the dominant taxa present in the OS, and there was a significant difference in the relative abundance of the bacterial phyla between the diabetic patients and control subjects. Proteobacteria were more abundant in the diabetic group, whereas Firmicutes was more abundant in the control group. Analysis of bacterial taxa at the genus level showed that the core microbiome of diabetic patients comprised Acinetobacter, Burkholderia, Sphingomonas, and Ralstonia, whereas that of the controls comprised Bradyrhizobiaceae, Staphylococcus, Corynebacterium, Pseudomonas, Novosphingobium, Neisseriaceae, and Acinetobacter. CONCLUSIONS: There was a significant difference in the microbial community composition between diabetic patients and healthy subjects. A high abundance of Acinetobacter in the OS of diabetic patients may arise from the unique characteristics of the OS compared with those of other organ surfaces.

Ocular Manifestations of Acquired Immunodeficiency Syndrome.

PURPOSE: To investigate the patterns and risk factors of the ocular manifestations of acquired immunodeficiency syndrome (AIDS) and their correlation with CD4+ count in the era of highly active antiretroviral therapy (HAART). METHODS: This retrospective study examined 127 AIDS patients who presented to Soonchunhyang University Hospital. Data were collected from patient interviews, clinical examinations, and laboratory investigations. Ophthalmologic examinations included the best-corrected visual acuity, intraocular pressure, anterior segment and adnexal examination, and dilated fundus examination. RESULTS: Of the 127 patients with AIDS, 118 were on HAART and 9 were not. The mean CD4+ count was 266.7 ± 209.1 cells/µL. There were ocular manifestations in 61 patients (48.0%). The incidence of anterior segment manifestations was higher than posterior segment manifestations at 28.3% and 19.7%, respectively. The mean CD4+ count was significantly (p < 0.05) lower in the patients with posterior versus anterior segment ocular manifestations. The most common ocular manifestation was retinal microvasculopathy (15.0%), followed by keratoconjunctivitis sicca (14.2%), conjunctival microvasculopathy (9.4%), cytomegalovirus retinitis (3.1%), herpes zoster ophthalmicus (2.4%), and blepharitis (1.6%). Retinal microvasculopathy and cytomegalovirus retinitis were common in patients with CD4+ counts <200 cells/µL, while keratoconjunctivitis sicca and conjunctival microvasculopathy were common in patients with CD4+ counts of 200 to 499 cells/µL. There was a significant (p < 0.05) association between ocular manifestation and CD4+ count or age. CONCLUSIONS: The introduction of HAART has changed the landscape of ocular presentations in patients with AIDS. In this study, anterior segment and external ocular manifestations occurred more frequently than posterior segment manifestations. Also, the mean CD4+ count was significantly lower in patients with posterior segment ocular manifestations versus anterior segment ocular manifestations. We found that CD4+ count and age >35 years were independent risk factors for developing ocular manifestations.

The effect of baicalin in a mouse model of retinopathy of prematurity.

Baicalin is a flavonoid derived from the dried root of Scutellaria baicalensis. In this study, oxygen-induced retinopathy was used to characterize the anti-angiogenic properties of baicalin in mice. Pups were exposed to a hyperbaric oxygen environment to induce retinal angiogenesis and were subjected to intraperitoneal injection of baicalin. Avascular area, neovascular tufts, and neovascular lumens were quantified from digital images. Compared to the vehicle, baicalin clearly reduced the central avascular zone and the number of neovascular tufts and lumens. High-dose baicalin (10 mg/kg) significantly reduced the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, angiotensin II, and vascular endothelial growth factor (VEGF). These results show that baicalin is a powerful antiangiogenic compound that attenuates new vessel formation in the retina after systemic administration, and is a candidate substance for therapeutic inhibition of retinal angiogenesis.

Correlation between Optic Nerve Parameters Obtained Using 3D Nonmydriatic Retinal Camera and Optical Coherence Tomography: Interobserver Agreement on the Disc Damage Likelihood Scale.

Purpose. To compare stereometric parameters obtained by three-dimensional (3D) optic disc photography and optical coherence tomography (OCT) and assess interobserver agreement on the disc damage likelihood scale (DDLS). Methods. This retrospective study included 190 eyes from 190 patients classified as normal, glaucoma suspect, or glaucomatous. Residents at different levels of training completed the DDLS for each patient before and after attending a training module. 3D optic disc photography and OCT were performed on each eye, and correlations between the DDLS and various parameters obtained by each device were calculated. Results. We found moderate agreement (weighted kappa value, 0.59 ± 0.03) between DDLS scores obtained by 3D optic disc photography and the glaucoma specialist. The weighted kappa values for agreement and interobserver concordance increased among residents after the training module. Interobserver concordance was the poorest at DDLS stages 5 and 6. The DDLS scored by the glaucoma specialist had the highest predictability value (0.941). Conclusions. The DDLS obtained by 3D optic disc photography is a useful diagnostic tool for glaucoma. A supervised teaching program increased trainee interobserver agreement on the DDLS. DDLS stages 5 and 6 showed the poorest interobserver agreement, suggesting that caution is required when recording these stages.

Sulodexide inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy.

Sulodexide is a mixed glycosaminoglycan composed of heparin and dermatan sulfate. In this study, the anti-angiogenic effect of sulodexide was investigated using an oxygen-induced retinopathy (OIR) mouse model. The retinas of sham-injected OIR mice (P17) had a distinctive central area of nonperfusion, and this area was significantly decreased in sulodexide-injected mice. The number of neovascular tufts measured by SWIFT_NV and mean neovascular lumen number were significantly decreased in sulodexide-injected mice. Hyperbaric oxygen exposure resulted in increased levels of VEGF, MMP-2 and MMP-9, and when mice were treated with sulodexide, a dose-dependent reduction in VEGF, MMP-2 and MMP-9 levels was observed. Our results clearly demonstrate the anti-angiogenic effect of sulodexide and highlight sulodexide as a candidate supplementary substance to be used for the treatment of ocular pathologies that involve neovascularization.

Evidence for neuroprotective effect of sulbutiamine against oxygen-glucose deprivation in rat hippocampal CA1 pyramidal neurons.

Hippocampus is one of the earliest brain regions that gets affected by ischemia, however, no pharmacological therapy exists yet that can fully counteract the ischemic damage. Here we study the effect of sulbutiamine, a synthetic thiamine analogue that can cross the blood-brain barrier easily, on hippocampal neurons under an in vitro model of ischemia, oxygen-glucose deprivation (OGD). We find that exposure to OGD in the presence of sulbutiamine significantly increases neuronal viability and enhances electrophysiological properties such as excitatory synaptic transmissions and intrinsic neuronal membrane input resistance in a concentration-dependent manner. Overall, here we report, for the first time, the neuroprotective evidence of sulbutiamine on hippocampal CA1 pyramidal neurons under OGD, which may have beneficial implications as a possible therapeutic agent/substance against ischemic insult.

Edible wild vegetable, Gymnaster koraiensis protects retinal ganglion cells against oxidative stress.

This study was conducted to determine whether Gymnaster koraiensis is effective at blunting the negative influence of N-methyl-D-aspartate (NMDA) on the retinas of rats and on oxidative stress induced cell death in transformed retinal ganglion cells (RGC-5). The ethyl acetate fraction of G. koraiensis (EAGK) and the isolated compound, 3,5-di-O-caffeoylquinic acid (3,5-DCQA), were shown to significantly attenuate the negative effect of H(2)O(2) on the RGC-5 cells tested by various procedures. The inclusion of EAGK or 3,5-DCQA in the culture reduced the reactive oxygen species (ROS) and replenished the reduced glutathione levels caused by various radical species such as H(2)O(2,) O(2)()(-) or ()OH. Moreover, EAGK or 3,5-DCQA inhibited lipid peroxidation caused by sodium nitroprusside (SNP) in rat brain homogenates. From in vivo experiments, the presence of NMDA in the retina affected the thickness of the inner plexiform layer (IPL) and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) in positive ganglion cells. EAGK or 3,5-DCQA protected the thinning of the IPL and increased TUNEL positive cells in the ganglion cell layer (GCL). Our results clearly demonstrate the neuroprotective effect of EAGK both in vitro and in vivo. Moreover, 3,5-DCQA is suggested to be the active compound of EAGK.

Sulbutiamine counteracts trophic factor deprivation induced apoptotic cell death in transformed retinal ganglion cells.

Sulbutiamine is a highly lipid soluble synthetic analogue of vitamin B(1) and is used clinically for the treatment of asthenia. The aim of our study was to demonstrate whether sulbutiamine is able to attenuate trophic factor deprivation induced cell death to transformed retinal ganglion cells (RGC-5). Cells were subjected to serum deprivation for defined periods and sulbutiamine at different concentrations was added to the cultures. Various procedures (e.g. cell viability assays, apoptosis assay, reactive oxygen species analysis, Western blot analysis, flow cytometric analysis, glutathione (GSH) and glutathione-S-transferase (GST) measurement) were used to demonstrate the effect of sulbutiamine. Sulbutiamine dose-dependently attenuated apoptotic cell death induced by serum deprivation and stimulated GSH and GST activity. Moreover, sulbutiamine decreased the expression of cleaved caspase-3 and AIF. This study demonstrates for the first time that sulbutiamine is able to attenuate trophic factor deprivation induced apoptotic cell death in neuronal cells in culture.

The compound isolated from the leaves of Phyllostachys nigra protects oxidative stress-induced retinal ganglion cells death.

This study was performed to determine whether the compound isolated from Phyllostachys nigra could attenuate oxidative stress in transformed retinal ganglion cells (RGC-5 cells) death. RGC-5 cells in culture were given two different insults such as l-buthionine-(S,R)-sulfoximine (BSO) plus glutamate for 24h or hydrogen peroxide for 24h, after which cell survival were measured. Among the four systematic fractions tested, ethyl acetate fraction showed a significantly higher inhibition which was in a concentration dependent manner. Eight compounds were isolated from ethyl acetate fraction of P. nigra using preparative RP-HPLC and Sephadex LH-20 column chromatography. Their chemical structures were elucidated by chemical and spectral analysis as isoorientin (1), orientin (2), vitexin (3), cis-coumaric acid (4), p-coumaric acid (5), luteolin 6-C-(6''-O-trans-caffeoylglucoside) (6), vittariflavone (7) and tricin (8). The luteolin 6-C-(6''-O-trans-caffeoylglucoside) (compound 6) significantly attenuated the negative effects of BSO plus glutamate or hydrogen peroxide to RGC-5 cells. Treatment of the RGC-5 cells with compound 6 reduced the reactive oxygen species (ROS) as quantified using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). This compound also replenished the reduced glutathione level. In conclusion, these results implicate that compound 6 isolated from P. nigra could be used as a leading compounds for retinal disease via anti-oxidative effects.

Stimulation of prostaglandin EP2 receptors on RGC-5 cells in culture blunts the negative effect of serum withdrawal.

Reduced neurotrophic support is one possible cause for retinal ganglion cells dying in glaucoma. Experiments were designed to investigate the effect of EP2 receptor agonist butaprost on transformed retinal ganglion (RGC-5) cells where reduced neurotrophic support was simulated by serum withdrawal. Cultures were analysed for cell viability, flow cytometry, reactive oxygen species and apoptosis. Western blot and immunohistochemistry were used to provide information for the occurrence of PGE(2) receptor-types. We demonstrated the existence of all four types of PGE(2) receptors in RGC-5 cells and exposure of cultures to butaprost resulted in an elevation of cAMP. Serum deprivation induced RGC-5 cell death was significantly attenuated by butaprost as well as by rolipram and forskolin where intracellular cAMP levels were increased. These data are of value in relation to the possible use of EP2 receptor agonists to reduce both elevated intraocular pressure and retinal ganglion cell death as occurs in glaucoma.

Correlation between disc damage likelihood scale and optical coherence tomography in the diagnosis of glaucoma.

PURPOSE: To investigate the relationship between the Disc Damage Likelihood Scale (DDLS), visual field and various optical coherence tomography (OCT) parameters for glaucoma diagnosis. METHODS: The study comprised 149 eyes from 149 patients. The patients were categorized as normal, glaucoma suspect or with glaucoma. They were clinically examined and graded according to the DDLS system. OCT was performed to acquire both a retinal nerve fibre layer analysis and an optic nerve head analysis. The relationships between DDLS score, visual field and OCT parameters were analysed using multiple correlation analysis. RESULTS: The normal, glaucoma suspect and glaucoma groups had average DDLS scores of 1.58 +/- 1.40, 2.55 +/- 1.93 and 5.33 +/- 1.39, respectively. Evaluating the area under the receiver operator characteristic curve, the DDLS had the best predictive power (0.917), followed by corrected pattern standard deviation. CONCLUSION: The DDLS is a useful parameter in the diagnosis of glaucoma and it showed a close correlation with visual field, cup/disc ratio and OCT parameters.

A prospective audit on the validity of written informed consent prior to glaucoma surgery: an Asian perspective.

PURPOSE: To assess the validity of written informed consent taken from patients prior to undergoing glaucoma surgery by testing their ability to understand the information offered to them during the consent-taking process. METHODS: Seventy-three patients were asked to complete a standardised confidential questionnaire after giving a written informed consent. Surgeons who were taking the consent were also requested to submit their self-evaluation form. Patients' understanding of the information they were given was evaluated using a standardised point scoring system. RESULTS: Fifty patients (68.5%) agreed that they were given enough time to make an informed decision, while 67 doctors (91.8%) claimed that they had allocated enough time to explain the procedures. Fifty-two patients (71.2%) reported that they were given adequate information on the details or diagnosis of their problems, 65 patients (89.0%) on the details of the procedure and 69 patients (94.5%) on the risks and complications. Thirty-four patients (46.6%) were not sure, or refused information on the risks and complications of the procedure. Only half of the patients (57.5%) had overall moderate understanding of their surgical problem, and only 13 patients (17.8%) were able to demonstrate a good overall understanding of their surgical problem. CONCLUSIONS: Although most patients acknowledged that they received sufficient information to give consent, few could objectively recall the information given to them. This study thus raises some doubts on the validity and quality of written informed consent, and highlights the importance of giving clear information to patients undergoing glaucoma surgery.

Effects of botulinum A toxin injection on the extraocular muscle fiber layers: comparison between subtenon injection and intramuscular injection.

PURPOSE: To compare the morphological changes following injection of botulinum A toxin to the extraocular muscle fiber layers with those following injection to the subtenon intramuscular system. METHODS: Twelve New Zealand white rabbits were divided into two groups. In the first group (six rabbits), four received injections of 10 units of botulinum A toxin into the subtenon space of the superior rectus muscle OD, and the same dose of botulinum A toxin was injected directly into the superior rectus muscle OS. The other two rabbits in the first group were labeled as control animals; 0.1 ml of normal saline was injected into the subtenon space OD, and direct intramuscular injection was performed on the opposite eye. The animals in the first group were killed after 4 weeks to measure the average diameter of the muscle fibers in both the orbital and global layer. In animals of the second group (six rabbits), the same procedures were performed and the animals were killed 12 weeks after treatment. RESULTS: The average diameter of muscle fibers in both the orbital layer and global layer was markedly reduced in all of the botulinum A toxin-injected groups at 4 weeks after treatment compared with the controls. There was no difference in the average diameter of the muscle fibers between the orbital layer of the subtenon-injected group and that of the intramuscular-injected group at 4 weeks after treatment, but the average diameter of the muscle fibers in the global layer was significantly reduced in the intramuscular-injected group compared with the subtenon-injected group at 4 weeks after treatment. At 12 weeks following treatment, there was no difference in the average diameter between the botulinum A toxin-injected group and the control group regardless of where the toxin was injected. CONCLUSION: Subtenon injection of botulinum A toxin induced similar morphological changes as direct intramuscular injection in the extraocular muscle fiber layers. These results suggest the possibility of clinical applications of subtenon botulinum A toxin injection for the treatment of strabismus.

The localization of PGE2 receptor subtypes in rat retinal cultures and the neuroprotective effect of the EP2 agonist butaprost.

It is concluded from immunohistochemical that all four types of prostaglandin-E(2) (PGE(2)) (EP1, EP2, EP3 and EP4) receptors are associated with specific cell-types in primary rat retinal cultures. Analysis specifically of EP2 receptor immunoreactivity shows it to coexist with some neurones expressing Thy-1 and calbindin immunoreactivities as well as with vimentin-positive Müller cells. Moreover, exposure of cultures to the EP2 specific agonist butaprost (100 nM) for a period of 24h results in a generation of cAMP thus providing support for the functionality of EP2 receptors. Cell survival was significantly affected in cultures where the serum concentration was reduced from 10 to 1% for 24h. This was reflected by a reduction in the number of GABA-positive neurons and an elevation of released lactate dehydrogenase (LDH) into the culture medium. Moreover, a number of cells displayed a clear generation of reactive oxygen species (ROS) and a staining for the breakdown of DNA by the TUNEL procedure as an indicator for apoptosis. These negative effects were attenuated when butaprost (100 nM) was present during the serum reduction and 30 min before the insult. The present studies provide evidence to show that all PGE(2) receptor types exist in the retina of rat pups, remain functional when the retinal cells are cultured and that specific activation of EP2 receptors with butaprost can attenuate a detrimental insult caused by insufficient serum that may occur in situ by reduced trophic support.