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Time- and dose-related effects of amyloid beta1-40 on retina and optic nerve morphology in rats

Mohd Lazaldin MA, Iezhitsa I, Agarwal R, Bakar NS, Agarwal P, Mohd Ismail N

Int J Neurosci, 2018 Oct;128(10):952-965.
PMID: 29488424 DOI: 10.1080/00207454.2018.1446953

PURPOSE: Amyloid beta (Aβ) is known to contribute to the pathophysiology of retinal neurodegenerative diseases such as glaucoma. Effects of intravitreal Aβ(1-42) on retinal and optic nerve morphology in animal models have widely been studied but not those of Aβ(1-40). Hence, we evaluated the time- and dose-related effects of intravitreal Aβ(1-40) on retinal and optic nerve morphology. Since oxidative stress and brain derived neurotrophic factor (BDNF) are associated with Aβ-induced neuronal damage, we also studied dose and time-related effects of Aβ(1-40) on retinal oxidative stress and BDNF levels.
MATERIALS AND METHODS: Five groups of rats were intravitreally administered with vehicle or Aβ(1-40) in doses of 1.0, 2.5, 5 and 10 nmol. Animals were sacrificed and eyes were enucleated at weeks 1, 2 and 4 post-injection. The retinae were subjected to morphometric analysis and TUNEL staining. Optic nerve sections were stained with toluidine blue and were graded for neurodegenerative effects. The estimation of BDNF and markers of oxidative stress in retina were done using ELISA technique.
RESULTS AND CONCLUSIONS: It was observed that intravitreal Aβ(1-40) causes significant retinal and optic nerve damage up to day 14 post-injection and there was increasing damage with increase in dose. However, on day 30 post-injection both the retinal and optic nerve morphology showed a trend towards normalization. The observations made for retinal cell apoptosis, retinal glutathione, superoxide dismutase activity and BDNF were in accordance with those of morphological changes with deterioration till day 14 and recovery by day 30 post-injection. The findings of this study may provide a guide for selection of appropriate experimental conditions for future studies.

Matched MeSH terms: Glaucoma
Fulltext Predictive factors of visual outcome of Malaysian cataract patients: a retrospective study

Thevi T, Godinho MA

Int J Ophthalmol, 2017;10(9):1452-1459.
PMID: 28944207 DOI: 10.18240/ijo.2017.09.19

AIM: To explore the associations between various characteristics of Malaysian cataract patients and their management, and their post-operative visual outcomes, to inform relevant bodies to reduce cataract-related blindness.

METHODS: We conducted a descriptive secondary data analysis of cataract surgery patients in Melaka Hospital, from 2007 to 2014 using the National Eye Database (NED). Patient-related factors (demographic features, systemic and ocular comorbidities) and management-related factors (surgical duration, type of surgery, type of lens) were analysed for their association with visual outcome (acuity).

RESULTS: Most patients were Malays (48.23%) and Chinese (38.55%) aged 60-79y (range 0-100y). Hypertension (58.61%) and diabetes (44.89%) were major systemic comorbidities. Glaucoma (6.71%) and diabetic retinopathy (10.12%) were the main ocular comorbidities. Other comorbidities were age-related macular degeneration, pterygium, corneal opacities, macula diseases, vitreous haemorrhage, retinal detachment and pseudoexfoliation (0.70%-1.60%). Preoperatively 7150 (55.03%) eyes presented with poor vision. Uncomplicated phacoemulsification performed quickly with foldable lenses gave good results.

CONCLUSION: Primary care physicians should initiate early detection to prevent late presentation of cataracts causing poor vision and should discuss the risks and benefits of cataract surgery while emphasizing the role of pre-existing comorbidities which may affect the visual outcomes. For good results, phacoemulsification should be done within 30min, without complications, using foldable posterior chamber intraocular lens.

Matched MeSH terms: Glaucoma
Effects of ranibizumab on the extracellular matrix production by human Tenon's fibroblast

Md Noh SM, Sheikh Abdul Kadir SH, Bannur ZM, Froemming GA, Abdul Hamid Hasani N, Mohd Nawawi H, et al.

Exp Eye Res, 2014 Oct;127:236-42.
PMID: 25139730 DOI: 10.1016/j.exer.2014.08.005

Anti-Vascular Endothelial Growth Factors (Anti-VEGF) agents have received recent interest as potential anti-fibrotic agents for their concurrent use with trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. The effects of this humanized monoclonal antibody on human Tenon's fibroblast (HTF), the key player of post trabeculectomy scar formation, are not fully understood. This study was conducted to understand the effects of ranibizumab on extracellular matrix production by HTF. The effect of ranibizumab on HTF proliferation and cell viability was determined using MTT assay (3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium). Ranibizumab at concentrations ranging from 0.01 to 0.5 mg/mL were administered for 24, 48 and 72 h in serum and serum free conditions. Supernatants and cell lysates from samples were assessed for collagen type 1 alpha 1 and fibronectin mRNA and protein level using quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). After 48-h, ranibizumab at 0.5 mg/mL, significantly induced cell death under serum-free culture conditions (p

Matched MeSH terms: Glaucoma, Open-Angle/surgery
Use of recombinant tissue plasminogen activator for treatment of recalcitrant anterior uveitis: A case series

Patrick S, Hui-Tze C, Wan-Hazabbah WH, Zunaina E, Azhany Y, Liza-Sharmini AT

J Taibah Univ Med Sci, 2018 Oct;13(5):483-487.
PMID: 31435366 DOI: 10.1016/j.jtumed.2018.03.005

Management of inflammation after surgery for recalcitrant anterior uveitis is challenging. Herein, we report successful treatment using intracameral injection of recombinant tissue plasminogen activator (rtPA) in two patients with recalcitrant anterior uveitis, due to infective uveitis and Vogt-Koyanagi-Harada disease, respectively. A 40-year-old woman presented with bilateral redness and vision reduction that had persisted 2 weeks. She also had bilateral anterior uveitis, vasculitis, retinitis, and optic disc swelling. Serology was positive for Bartonella henselae and Toxoplasma gondii. She was treated using long-term systemic corticosteroids and appropriate antibiotics. Our second case; a healthy 30-year-old man with bilateral eye redness and reduced vision without pain, and associated with headache and tinnitus for 1 weeks. He showed bilateral granulomatous inflammation with vitritis, choroiditis, retinitis, and hyperemic optic disc. The patient was diagnosed with Vogt-Koyanagi-Harada disease and treated with systemic corticosteroids. Both patients developed secondary cataracts and glaucoma that necessitated surgical intervention. Persistent chronic inflammation led to the formation of a thick fibrin membrane anterior to the intraocular lens (IOL) after phacoemulsification surgery with IOL implantation. This membrane was removed surgically, and intracameral injection of rtPA (25 μg) was carried out. The persistent inflammation had resolved and visual acuity had significantly improved within 1 week of intracameral rtPA injection. There were no reported ocular or systemic side effects. Intracameral rtPA is beneficial in patients with recalcitrant anterior uveitis who have undergone intraocular surgery. In most cases, surgical intervention improves the patients' vision. Intracameral rtPA should be considered in cases of persistent inflammation of varying etiology.

Matched MeSH terms: Glaucoma
Microvascular endothelial function and severity of primary open angle glaucoma

Bukhari SM, Kiu KY, Thambiraja R, Sulong S, Rasool AH, Liza-Sharmini AT

Eye (Lond), 2016 Dec;30(12):1579-1587.
PMID: 27540832 DOI: 10.1038/eye.2016.185

PurposeThe role of microvascular endothelial dysfunction on severity of primary open angle glaucoma (POAG) was investigated in this study.Patients and methodsA prospective cohort study was conducted. One hundred and fourteen ethnically Malay patients (114 eyes) with POAG treated at the eye clinic of Hospital University Sains Malaysia between April 2012 and December 2014 were recruited. Patients aged between 40 and 80 years with two consecutive reliable and reproducible Humphrey visual field 24-2 analyses were selected. Patients who were diagnosed with any other type of glaucoma, previous glaucoma-filtering surgery, or other surgeries except uncomplicated cataract and pterygium surgery were excluded. Humphrey visual field analysis 24-2 was used to stratify the severity of glaucoma using Advanced Glaucoma Intervention Study (AGIS) score at the time of recruitment. Microvascular endothelial function was assessed using Laser Doppler fluximetry and iontophoresis. Iontophoresis process with acetylcholine (ACh) and sodium nitroprusside (SNP) was used to measure microvascular endothelium-dependent and -independent vasodilatation, respectively.ResultsBased on the AGIS score, 55 patients showed mild glaucoma, with 29 moderate and 30 severe. There was statistically significant difference in microvascular endothelial function (ACh% and AChmax) between mild and moderate POAG cases (P=0.023) and between mild and severe POAG cases (P<0.001). There was negative correlation between microvascular endothelial function and severity of POAG (r=-0.457, P<0.001).ConclusionMicrovascular endothelial dysfunction may have a role in influencing the severity of POAG in Malay patients.

Study site: Eye clinic Hospital Universiti Sains Malaysia (HUSM)

Matched MeSH terms: Glaucoma, Open-Angle
Newer targets for modulation of intraocular pressure: focus on adenosine receptor signaling pathways

Agarwal R, Agarwal P

Expert Opin Ther Targets, 2014 May;18(5):527-39.
PMID: 24579961 DOI: 10.1517/14728222.2014.888416

The homeostatic role of adenosine in regulating intraocular pressure (IOP) is now widely recognized, and hence, the drugs targeting adenosine receptors have become the focus of investigation. In this review, we summarize the adenosine receptor signaling pathways, which could be potential therapeutic targets for the management of glaucoma.

Matched MeSH terms: Glaucoma/drug therapy*; Glaucoma/physiopathology