Tengku Ain Kamalden

Light- and sodium azide-induced death of RGC-5 cells in culture occurs via different mechanisms.

Previous studies have shown that light impinging on the retina in situ has the capacity to kill neuronal and non-neuronal cells in vitro by interacting directly with mitochondrial constituents. A number of fluorophores are associated with mitochondria which can potentially absorb different wave-lengths of light, including cytochrome oxidase. The aim of the present study was to compare the death mechanism of a light insult to RGC-5 cells in culture with that of sodium azide. Sodium azide’s main toxic action is in inhibiting the function of cytochrome oxidase in the mitochondrial electron transport chain. Our studies showed that light and sodium azide kill RGC-5 cells via different mechanisms although some similarities do occur. Both inducers of cell death caused the generation of reactive oxygen species (ROS), the expression of phosphatidylserine, the breakdown of DNA and the activation of p38 MAPK, resulting in its translocation from the nucleus to the cytoplasm. However, light-induced cell death occurs via necroptosis, in that it was inhibited by necrostatin-1 and was caspase-independent. This was not the case for sodium azide, where the death process was caspase-dependent, occurred via apoptosis and was unaffected by necrostatin-1. Moreover, light caused an activation of the apoptosis inducing factor (AIF), c-Jun, JNK and HO-1, but it did not affect alpha fodrin or caspase-3. In contrast, sodium azide caused the activation of alpha fodrin and the stimulation of caspase-3 content without influencing AIF, c-Jun, JNK or HO-1. Therefore we conclude that light does not have a specific action on cytochrome oxidase in mitochondria to cause cell death.

CAFFEIC ACID PHENETHYL ESTER (CAPE): SCAVENGER OF PEROXYNITRITE IN VITRO AND IN SEPSIS MODELS

ABSTRACT Excessive free radical production by immune cells has been linked to cell death and tissue injury during sepsis. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death that has been identified in several pathological conditions. Caffeic acid phenethyl ester (CAPE) is an active component of honeybee products and exhibits antioxidant, anti-inflammatory, and immunomodulatory activities. The present study examined the ability of CAPE to scavenge peroxynitrite in RAW 264.7 murine macrophages stimulated with lipopolysaccharide/interferon-&ggr; that was used as an in vitro model. Conversion of 123-dihydrorhodamine to its oxidation product 123-rhodamine was used to measure peroxynitrite production. Two mouse models of sepsis (endotoxemia and cecal ligation and puncture) were used as in vivo models. The level of serum 3-nitrotyrosine was used as an in vivo marker of peroxynitrite. The results demonstrated that CAPE significantly improved the viability of lipopolysaccharide/interferon-&ggr;–treated RAW 264.7 cells and significantly inhibited nitric oxide production, with effects similar to those observed with an inhibitor of inducible nitric oxide synthase (1400W). In addition, CAPE exclusively inhibited the synthesis of peroxynitrite from the artificial substrate SIN-1 and directly prevented the peroxynitrite-mediated conversion of dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In both sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as evidenced by the absence of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite. Thus, CAPE attenuates the inflammatory responses that lead to cell damage and, potentially, cell death through suppression of the production of cytotoxic molecules such as nitric oxide and peroxynitrite. These observations provide evidence of the therapeutic potential of CAPE treatment for a wide range of inflammatory disorders.

Bone Remodeling in Choroidal Osteoma Monitored by Fundus Photography and Spectral-Domain Optical Coherence Tomography

Choroidal osteoma is a benign ossifying tumor of the choroid, consisting of mature bone tissue. It has been described to enlarge and evolve at varying rates over time. Here, we report and quantify the progression of a unilateral choroidal osteoma in a 7-year-old boy by fundus photography, and document tumor remodeling by spectral domain optical coherence tomography images.

Genistein Blunts the Negative Effect of Ischaemia to the Retina Caused by an Elevation of Intraocular Pressure

Aims: Deduce whether the isoflavone genistein blunts the effect of ischaemia to the retina. Methods: Ischaemia was induced in rats by raising the intraocular pressure (120 mm Hg) for 50 min. Genistein (10 mg/kg) was injected intraperitoneally 1 h before and after ischaemia. Seven days after ischaemia, the level of mRNAs for neurofilament light (NF-L), caspase 3, caspase 8, glial fibrillary acidic protein (GFAP), poly-ADP ribose polymerase (PARP), Thy-1 and proteins (GFAP, NF-L, PARP) in whole retinas were determined. NF-L and tubulin proteins in optic nerves were also determined. Retinas were also processed for the localization of choline acetyltransferase (ChAT) and GFAP immunoreactivities. Results: Ischaemia caused a significant reduction in ganglion cell proteins in the optic nerve (NF-L and tubulin) and retina (NF-L). Retinal Thy-1 (mRNA and protein) and NF-L (mRNA) were also reduced while mRNAs of caspase 3, caspase 8, PARP and GFAP (also protein) were increased. Changes in the mRNAs and proteins induced by ischaemia were significantly blunted by genistein with the exception of the increase in GFAP and PARP protein/mRNA levels. Ischaemia-induced changes in the localization of ChAT were also clearly attenuated by genistein treatment. Conclusions: Genistein blunts most of the damaging effects caused to the retina by ischaemia.

Ectopic Cerebrospinal-like Fluid From Retrobulbar Cysts as a Possible Cause of Pediatric Retinal Detachment Associated With Optic Disc Coloboma: New Implications for Management

Retinal detachment in adults with posterior segment coloboma is thought to be rhegmatogenous. Vitrectomy techniques are therefore used therapeutically. There is indirect evidence that subretinal fluid in retinal detachment, associated with optic nerve cavitation, is cerebrospinal fluid (CSF). We report 2 pediatric cases, referred for the management of coloboma-related retinal detachment, that provide direct evidence that the fluid is like CSF.

Endoscopic transnasal removal of an intraconal foreign body using an image-guided surgical system

Abstract Foreign bodies lodged in the intraconal space of the orbit pose a surgical challenge due to its deep location behind the globe. Image-guided endoscopic transnasal surgery facilitates the localization of the metallic foreign bodies and enables its safe removal with minimal surrounding tissue damage and optic nerve injury.

Advanced glycation end products-related modulation of cathepsin L and NF-κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα

The retinal pigment epithelium (RPE) plays a central role in neuroretinal homoeostasis throughout life. Altered proteolysis and inflammatory processes involving RPE contribute to the pathophysiology of age‐related macular degeneration (AMD), but the link between these remains elusive. We report for the first time the effect of advanced glycation end products (AGE)—known to accumulate on the ageing RPEs underlying Bruchs membrane in situ—on both key lysosomal cathepsins and NF‐κB signalling in RPE. Cathepsin L activity and NF‐κB effector levels decreased significantly following 2‐week AGE exposure. Chemical cathepsin L inhibition also decreased total p65 protein levels, indicating that AGE‐related change of NF‐κB effectors in RPE cells may be modulated by cathepsin L. However, upon TNFα stimulation, AGE‐exposed cells had significantly higher ratio of phospho‐p65(Ser536)/total p65 compared to non‐AGEd controls, with an even higher fold increase than in the presence of cathepsin L inhibition alone. Increased proportion of active p65 indicates an AGE‐related activation of NF‐κB signalling in a higher proportion of cells and/or an enhanced response to TNFα. Thus, NF‐κB signalling modulation in the AGEd environment, partially regulated via cathepsin L, is employed by RPE cells as a protective (para‐inflammatory) mechanism but renders them more responsive to pro‐inflammatory stimuli.

The epidemiology of Open Globe Injuries presenting to a tertiary referral eye hospital in Australia

BACKGROUND Open globe injuries (OGIs) account for 44% of the cost of ocular trauma within Australia. It is estimated that 90% of ocular trauma is preventable. However, there have been few epidemiological studies within Australia that have identified groups at risk of OGIs specifically. The aim of our study was to review the epidemiology of OGIs presenting to a tertiary referral eye hospital in Australia. METHODS The Birmingham Eye Trauma Terminology (BETT) system was used to classify injuries as globe ruptures, penetrating eye injuries (PEIs), intraocular foreign bodies (IOFBs) or perforating injuries. Demographic data, past ocular history, mechanism of trauma, ocular injuries, and best-corrected visual acuity (BCVA) before and after treatment were recorded. RESULTS The 205 OGIs included 80 globe ruptures, 71 PEIs, 48 IOFBs and six perforating injuries. Falls predominated in older age groups compared to the other mechanisms of injury (p<0.0001). A fall was responsible for 33 globe ruptures and 82% of these had a history of previous intraocular surgery. Globe rupture and perforating injuries had poorer visual outcomes (p<0.05), consistent with previous studies. Alcohol was implicated in 20 cases of OGI, with 11 of these due to assault. PEIs and IOFBs commonly occurred while working with metal. BCVA was significantly worse following removal of an intraocular foreign body. We found presenting BCVA to be a good predictor of BCVA at the time of discharge. CONCLUSIONS The causes of OGI varied in association with age, with older people mostly incurring their OGI through falls and younger adults through assault and working with metal. Globe ruptures occurring after a fall often had a history of intraocular surgery. The initial BCVA is useful for non-ophthalmologists who are unfamiliar with the ocular trauma score to help predict the BCVA following treatment.

Effect of Nocturnal Intermittent Peritoneal Dialysis on Intraocular Pressure and Anterior Segment Optical Coherence Tomography Parameters.

Purpose: To evaluate the effect of nocturnal intermittent peritoneal dialysis (NIPD) on intraocular pressure (IOP) and anterior segment optical coherence tomography (ASOCT) parameters. Systemic changes associated with NIPD were also analyzed. Methods: Observational study. Nonglaucomatous patients on NIPD underwent systemic and ocular assessment including mean arterial pressure (MAP), body weight, serum osmolarity, visual acuity, IOP measurement, and ASOCT within 2 hours both before and after NIPD. The Zhongshan Angle Assessment Program (ZAAP) was used to measure ASOCT parameters including anterior chamber depth, anterior chamber width, anterior chamber area, anterior chamber volume, lens vault, angle opening distance, trabecular-iris space area, and angle recess area. T tests and Pearson correlation tests were performed with P<0.05 considered statistically significant. Results: A total of 46 eyes from 46 patients were included in the analysis. There were statistically significant reductions in IOP (−1.8±0.6 mm Hg, P=0.003), MAP (−11.9±3.1 mm Hg, P<0.001), body weight (−0.7±2.8 kg, P<0.001), and serum osmolarity (−3.4±2.0 mOsm/L, P=0.002) after NIPD. All the ASOCT parameters did not have any statistically significant changes after NIPD. There were no statistically significant correlations between the changes in IOP, MAP, body weight, and serum osmolarity (all P>0.05). Conclusions: NIPD results in reductions in IOP, MAP, body weight, and serum osmolarity in nonglaucomatous patients.

The next generation of diagnostic biomarkers for type 2 diabetes

Diabetes is a major cause of morbidity and mortality in both the United States and Asia. The greatest public health impact of diabetes is its vascular complications, which include both microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular (ischemic heart disease, cerebrovascular disease, peripheral vascular disease) processes. Given that the diabetes epidemic continues to grow worldwide, there is a clear need for improvements in the management of the disease and its complications. The identification of biomarkers and pathogenic determinants of progression not only could provide tools physicians could use to monitor disease progression but could also give important insights into the mechanisms behind diabetic vascular complications, thus potentially opening new avenues for treatment.