Displaying publications 21 - 34 of 34 in total

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  1. Jackson N, Reddy SC, Hishamuddin M, Low HC
    Clin Lab Haematol, 1996 Jun;18(2):105-9.
    PMID: 8866143
    The associations between retinal findings and haematological parameters in acute leukaemia are controversial. Sixty-three newly-diagnosed acute leukaemia patients, aged 12-77 years, were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton wool spots (CWS) and macular haemorrhages (MH), Thirty-three patients (52.4%) showed at least one retinal abnormality. The prevalence of individual findings was: IRH (30 cases), WCH (20 cases), CWS (5 cases), MH (11 cases). In contrast to previous studies, there was no association between any of these retinal findings and the haemoglobin level or the platelet count. There was a higher median WBC in patients with IRH (68 x 10(9)/l) than in those without IRH (15.4 x 10(9)/l), P = 0.037. When the acute myeloblastic leukaemia cases were considered separately, an association was also found between higher WBC and the presence of WCH and CWS. There was no association between retinal findings and FAB type in the AML cases. We conclude that a high WBC may be at least as important as anaemia and thrombocytopenia in the pathogenesis of the retinopathy of acute leukaemia.
    Matched MeSH terms: Retina/pathology*
  2. Reddy SC, Jackson N
    Acta Ophthalmol Scand, 2004 Feb;82(1):81-5.
    PMID: 14738490
    PURPOSE: To determine the prevalence of retinal changes in newly diagnosed acute leukaemia patients, and to establish the relationship between retinal lesions and haematological parameters in these patients.

    METHODS: A total of 127 patients with acute leukaemia (myeloid and lymphoid), of both genders, aged between 13 and 77 years, were examined by an ophthalmologist for retinal changes using direct/indirect ophthalmoscopy within 2 days of diagnosis before starting chemotherapy.

    RESULTS: Retinal lesions were seen in 62 cases (49%), with intraretinal haemorrhages being the most common lesion (42%). A high white blood cell count was significantly associated with intraretinal haemorrhages (p = 0.04) and white-centred haemorrhages (p = 0.001), while a low platelet count was significantly associated with intraretinal haemorrhages (p = 0.03) in acute myeloid leukaemia patients.

    CONCLUSIONS: A high white blood cell count may be considered as important as a low platelet count in the pathogenesis of leukaemic retinopathy.

    Matched MeSH terms: Retina/pathology*
  3. Sng CC, Wong WL, Cheung CY, Lee J, Tai ES, Wong TY
    J Hypertens, 2013 Oct;31(10):2036-42.
    PMID: 23787404 DOI: 10.1097/HJH.0b013e328362c201
    OBJECTIVE(S): To examine the effect of blood pressure (BP) on retinal vascular fractal dimension (Df), a measure of microvascular network complexity and density in a multiethnic cohort.
    METHODS: A population-based study of 3876 Chinese, Malay and Indian participants in Singapore. Retinal Df was measured using a computer-based program from digital retinal photographs. Associations between retinal Df and mean arterial BP (MABP) in the whole cohort and in each racial group were analysed using linear regression analysis. Logistic regression was used to examine the association between retinal Df and hypertension status.
    RESULTS: The mean retinal Df of the study population was 1.45 (standard deviation 0.03). After adjustment for age, sex, race, diabetes, BMI, cholesterol and creatinine levels, persons with smaller Df had higher MABP (mean difference MABP was 6.18 mmHg comparing lowest to highest Df quartiles, P<0.001). This was similar in Chinese, Malay and Indian persons [mean difference 6.40 (P<0.001), 4.72 (P=0.011) and 6.62 (P<0.001)mmHg, respectively]. Persons with smaller retinal Df were more likely to have uncontrolled treated or untreated hypertension [odds ratio 1.79 (P=0.003) and 2.60 (P=0.003), respectively, comparing lowest to highest Df quartiles] than those with no hypertension; this relationship was not seen comparing persons with controlled treated hypertension with no hypertension (odds ratio 1.01, P=0.972).
    CONCLUSION: Hypertension was associated with a sparser retinal vascular network, which was similar across different racial/ethnic groups and most apparent in those with uncontrolled or untreated hypertension. These data suggest that microvascular remodelling can be quantified by measuring retinal vasculature.
    Matched MeSH terms: Retina/pathology
  4. Sadikan MZ, Nasir NAA, Agarwal R, Ismail NM
    Biomolecules, 2020 04 05;10(4).
    PMID: 32260544 DOI: 10.3390/biom10040556
    : Oxidative stress plays an important role in retinal neurodegeneration and angiogenesis associated with diabetes. In this study, we investigated the effect of the tocotrienol-rich fraction (TRF), a potent antioxidant, against diabetes-induced changes in retinal layer thickness (RLT), retinal cell count (RCC), retinal cell apoptosis, and retinal expression of vascular endothelial growth factor (VEGF) in rats. Additionally, the efficacy of TRF after administration by two different routes was compared. The diabetes was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin. Subsequently, diabetic rats received either oral or topical treatment with vehicle or TRF. Additionally, a group of non-diabetic rats was included with either oral or topical treatment with a vehicle. After 12 weeks of the treatment period, rats were euthanized, and retinas were collected for measurement of RLT, RCC, retinal cell apoptosis, and VEGF expression. RLT and RCC in the ganglion cell layer were reduced in all diabetic groups compared to control groups (p < 0.01). However, at the end of the experimental period, oral TRF-treated rats showed a significantly greater RLT compared to topical TRF-treated rats. A similar observation was made for retinal cell apoptosis and VEGF expression. In conclusion, oral TRF supplementation protects against retinal degenerative changes and an increase in VEGF expression in rats with streptozotocin-induced diabetic retinopathy. Similar effects were not observed after topical administration of TRF.
    Matched MeSH terms: Retina/pathology*
  5. Chan JCY, Chee ML, Tan NYQ, Cheng CY, Wong TY, Sabanayagam C
    Nutr Diabetes, 2018 03 07;8(1):16.
    PMID: 29549238 DOI: 10.1038/s41387-018-0018-0
    AIMS: To examine the association of body mass index (BMI) with the incidence of diabetes mellitus (DM) and diabetic retinopathy (DR) in Asians.

    METHODS: We analysed data from 4101 adults (Malay, n = 1901 and Indian, n = 2200) who participated in the baseline (2004-2009) and 6-year follow-up (2011-2015) of two independent population-based studies with similar methodology in Singapore. BMI was categorised into normal (<25 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). DM was diagnosed as random plasma glucose ≥200 mg/dL, HbA1c ≥6.5% or self-reported physician diagnosed DM. DR was assessed from retinal photographs graded using a standard protocol. The associations of baseline BMI with incident DM and DR was examined using multivariable poisson regression models adjusting for potential confounders including duration of DM, family history of DM and HbA1c.

    RESULTS: The incidence of DM was 12.8% and among 1586 participants with DM, the incidence of DR was 17.6% over a median follow-up period of 6.2 years. Compared to those with BMI 

    Matched MeSH terms: Retina/pathology
  6. Mohamad NA, Ramachandran V, Ismail P, Mohd Isa H, Chan YM, Ngah NF, et al.
    Bosn J Basic Med Sci, 2018 Aug 01;18(3):260-267.
    PMID: 29579408 DOI: 10.17305/bjbms.2018.2493
    Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49) and non-responder (n = 84) group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018). Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05). Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.
    Matched MeSH terms: Retina/pathology
  7. Mat Nor N, Guo CX, Rupenthal ID, Chen YS, Green CR, Acosta ML
    Invest Ophthalmol Vis Sci, 2018 07 02;59(8):3682-3693.
    PMID: 30029255 DOI: 10.1167/iovs.17-22829
    Purpose: To evaluate the long-term effect on inflammation and inflammasome activation of intravitreally delivered connexin43 mimetic peptide (Cx43MP) in saline or incorporated within nanoparticles (NPs) for the treatment of the light-damaged rat eye.

    Methods: Light-induced damage to the retina was created by exposure of adult albino Sprague-Dawley rats to intense light for 24 hours. A single dose of Cx43MP, Cx43MP-NPs, or saline was injected intravitreally at 2 hours after onset of light damage. Fluorescein isothiocyanate (FITC)-labelled Cx43MP-NPs were intravitreally injected to confirm delivery into the retina. Electroretinogram (ERG) recordings were performed at 24 hours, 1 week, and 2 weeks post cessation of light damage. The retinal and choroidal layers were analyzed in vivo using optical coherence tomography (OCT) and immunohistochemistry was performed on harvested tissues using glial fibrillary acidic protein (GFAP), leukocyte common antigen (CD45), and Cx43 antibodies.

    Results: FITC was visualized 30 minutes after injection in the ganglion cell layer and in the choroid. Cx43MP and Cx43MP-NP treatments improved a-wave and b-wave function of the ERG compared with saline-injected eyes at 1 week and 2 weeks post treatment, and prevented photoreceptor loss by 2 weeks post treatment. Inflammation was also reduced and this was in parallel with downregulation of Cx43 expression.

    Conclusions: The slow release of Cx43MP incorporated into NPs is more effective at treating retinal injury than a single dose of native Cx43MP in solution by reducing inflammation and maintaining both retinal structure and function. This NP preparation has clinical relevance as it reduces possible ocular complications associated with repeated intravitreal injections.

    Matched MeSH terms: Retina/pathology*
  8. Mohd Khalid MK, Yakob Y, Md Yasin R, Wee Teik K, Siew CG, Rahmat J, et al.
    Mol Vis, 2015;21:1185-90.
    PMID: 26539030
    The availability of molecular genetic testing for retinoblastoma (RB) in Malaysia has enabled patients with a heritable predisposition to the disease to be identified, which thus improves the clinical management of these patients and their families. In this paper, we presented our strategy for performing molecular genetic testing of the RB1 gene and the findings from our first 2 years of starting this service.
    Matched MeSH terms: Retina/pathology
  9. Mat Nor MN, Rupenthal ID, Green CR, Acosta ML
    Neurotherapeutics, 2020 Jan;17(1):371-387.
    PMID: 31637594 DOI: 10.1007/s13311-019-00786-5
    Increased Connexin43 hemichannel opening is associated with inflammasome pathway activation and inflammation in a range of pathologies including ocular disorders, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). In this study, the effect on retinal function and morphology of clinically safe doses of orally delivered tonabersat, a small molecule connexin hemichannel blocker, was investigated in the light-damaged retina animal model of dry AMD and in a spontaneous rat model of DR. Clinical parameters (fundus imaging, optical coherence tomography (OCT), and electroretinography) and inflammatory markers (immunohistochemistry for Iba-1 microglial marker, astrocyte marker glial fibrillary acidic protein, and Connexin43 protein expression) were assessed. Tonabersat treatment reduced inflammation in the retina in parallel with preservation of retinal photoreceptor function when assessed up to 3 months post light damage in the dry AMD model. In the DR model, clinical signs, including the presence of aneurysms confirmed using Evans blue dye perfusion, were reduced after daily tonabersat treatment for 2 weeks. Inflammation was also reduced and retinal electrical function restored. Tonabersat regulates assembly of the inflammasome (NLRP3) through Connexin43 hemichannel block, with the potential to reduce inflammation, restore vascular integrity and improve anatomical along with some functional outcomes in retinal disease.
    Matched MeSH terms: Retina/pathology
  10. Kim Y, Griffin JM, Nor MNM, Zhang J, Freestone PS, Danesh-Meyer HV, et al.
    Neurotherapeutics, 2017 Oct;14(4):1148-1165.
    PMID: 28560708 DOI: 10.1007/s13311-017-0536-9
    The cis benzopyran compound tonabersat (SB-220453) has previously been reported to inhibit connexin26 expression in the brain by attenuating the p38-mitogen-activated protein kinase pathway. We show here that tonabersat directly inhibits connexin43 hemichannel opening. Connexin43 hemichannels have been called "pathological pores" based upon their role in secondary lesion spread, edema, inflammation, and neuronal loss following central nervous system injuries, as well as in chronic inflammatory disease. Both connexin43 hemichannels and pannexin channels released adenosine triphosphate (ATP) during ischemia in an in vitro ischemia model, but only connexin43 hemichannels contributed to ATP release during reperfusion. Tonabersat inhibited connexin43 hemichannel-mediated ATP release during both ischemia and reperfusion phases, with direct channel block confirmed using electrophysiology. Tonabersat also reduced connexin43 gap junction coupling in vitro, but only at higher concentrations, with junctional plaques internalized and degraded via the lysosomal pathway. Systemic delivery of tonabersat in a rat bright-light retinal damage model (a model for dry age-related macular degeneration) resulted in significantly improved functional outcomes assessed using electroretinography. Tonabersat also prevented thinning of the retina, especially the outer nuclear layer and choroid, assessed using optical coherence tomography. We conclude that tonabersat, already given orally to over 1000 humans in clinical trials (as a potential treatment for, and prophylactic treatment of, migraine because it was thought to inhibit cortical spreading depression), is a connexin hemichannel inhibitor and may have the potential to be a novel treatment of central nervous system injury and chronic neuroinflammatory disease.
    Matched MeSH terms: Retina/pathology
  11. Razali N, Agarwal R, Agarwal P, Kapitonova MY, Kannan Kutty M, Smirnov A, et al.
    Eur J Pharmacol, 2015 Feb 15;749:73-80.
    PMID: 25481859 DOI: 10.1016/j.ejphar.2014.11.029
    Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.
    Matched MeSH terms: Retina/pathology
  12. Razali N, Agarwal R, Agarwal P, Tripathy M, Kapitonova MY, Kutty MK, et al.
    Exp Eye Res, 2016 Feb;143:9-16.
    PMID: 26424219 DOI: 10.1016/j.exer.2015.09.014
    Steroid-induced hypertension and glaucoma is associated with increased extracellular meshwork (ECM) deposition in trabecular meshwork (TM). Previous studies have shown that single drop application of trans-resveratrol lowers IOP in steroid-induced ocular hypertensive (SIOH) rats. This IOP lowering is attributed to activation of adenosine A1 receptors, which may lead to increased matrix metalloproteinase (MMP)-2 activity. This study evaluated the effect of repeated topical application of trans-resveratrol for 21 days in SIOH animals on IOP, changes in MMP-2 level in aqueous humor, trabecular meshwork and retinal morphology and retinal redox status. We observed that treatment with trans-resveratrol results in significant and sustained IOP reduction in SIOH rats. This IOP reduction is associated with significantly higher aqueous humor total MMP-2 level; significantly reduced TM thickness and increased number of TM cells. Treatment with trans-resveratrol also significantly increased ganglion cell layer (GCL) thickness, the linear cell density in the GCL and inner retina thickness; and significantly reduced retinal oxidative stress compared to the SIOH vehicle-treated group. In conclusion, repeated dose topical application of trans-resveratrol produces sustained IOP lowering effect, which is associated with increased level of aqueous humor MMP-2, normalization of TM and retinal morphology and restoration of retinal redox status.
    Matched MeSH terms: Retina/pathology*
  13. Lim CC, Lee WL, Leo YS, Lee KE, Chan KP, Ling AE, et al.
    J Neurol Neurosurg Psychiatry, 2003 Jan;74(1):131-3.
    PMID: 12486285
    The Nipah virus is a newly identified paramyxovirus responsible for an outbreak of fatal encephalitis in Malaysia and Singapore. This paper reports the follow up clinical and magnetic resonance imaging findings in 22 affected subjects. Of 13 patients with encephalitis, one died, one was lost to follow up, and seven recovered. Among the four remaining patients, one had residual sixth nerve palsy, another suffered from severe clinical depression, and a third patient had evidence of retinal artery occlusion. One patient with delayed onset Horner syndrome had a single lesion in the cervical spinal cord. The brain magnetic resonance findings were stable or improved in nine patients over 18 months of follow up. Among a second group of nine asymptomatic seropositive abattoir workers, magnetic resonance examination in seven subjects revealed discrete small lesions in the brain; similar to those detected in encephalitis patients. These findings suggest that in addition to encephalitis, the newly discovered Nipah virus affects the spinal cord and the retina. Late clinical and radiological findings can occur in Nipah virus infections as with other paramyxoviruses.
    Matched MeSH terms: Retina/pathology
  14. Mat Nor MN, Rupenthal ID, Green CR, Acosta ML
    Int J Mol Sci, 2021 Feb 10;22(4).
    PMID: 33578721 DOI: 10.3390/ijms22041755
    Dysregulation of retinal function in the early stages of light-induced retinal degeneration involves pannexins and connexins. These two types of proteins may contribute to channels that release ATP, leading to activation of the inflammasome pathway, spread of inflammation and retinal dysfunction. However, the effect of pannexin channel block alone or block of both pannexin channels and connexin hemichannels in parallel on retinal activity in vivo is unknown. In this study, the pannexin channel blocker probenecid and the connexin hemichannel blocker tonabersat were used in the light-damaged rat retina. Retinal function was evaluated using electroretinography (ERG), retinal structure was analyzed using optical coherence tomography (OCT) imaging and the tissue response to light-induced injury was assessed immunohistochemically with antibodies against glial fibrillary acidic protein (GFAP), Ionized calcium binding adaptor molecule 1 (Iba-1) and Connexin43 (Cx43). Probenecid did not further enhance the therapeutic effect of connexin hemichannel block in this model, but on its own improved activity of certain inner retina neurons. The therapeutic benefit of blocking connexin hemichannels was further evaluated by comparing these data against results from our previously published studies that also used the light-damaged rat retina model. The analysis showed that treatment with tonabersat alone was better than probenecid alone at restoring retinal function in the light-damaged retina model. The results assist in the interpretation of the differential action of connexin hemichannel and pannexin channel therapeutics for potential treatment of retinal diseases.
    Matched MeSH terms: Retina/pathology
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