PMID- 29488424 OWN - NLM STAT- MEDLINE DCOM- 20181221 LR - 20181221 IS - 1563-5279 (Electronic) IS - 0020-7454 (Linking) VI - 128 IP - 10 DP - 2018 Oct TI - Time- and dose-related effects of amyloid beta1-40 on retina and optic nerve morphology in rats. PG - 952-965 LID - 10.1080/00207454.2018.1446953 [doi] AB - PURPOSE: Amyloid beta (Abeta) is known to contribute to the pathophysiology of retinal neurodegenerative diseases such as glaucoma. Effects of intravitreal Abeta(1-42) on retinal and optic nerve morphology in animal models have widely been studied but not those of Abeta(1-40). Hence, we evaluated the time- and dose-related effects of intravitreal Abeta(1-40) on retinal and optic nerve morphology. Since oxidative stress and brain derived neurotrophic factor (BDNF) are associated with Abeta-induced neuronal damage, we also studied dose and time-related effects of Abeta(1-40) on retinal oxidative stress and BDNF levels. MATERIALS AND METHODS: Five groups of rats were intravitreally administered with vehicle or Abeta(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 Abeta(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. FAU - Mohd Lazaldin, Mohd Aizuddin AU - Mohd Lazaldin MA AUID- ORCID: 0000-0002-7727-6043 AD - a Centre For Neuroscience Research, Faculty of Medicine , Universiti Teknologi MARA, Sungai Buloh Campus, Selangor , Malaysia. FAU - Iezhitsa, Igor AU - Iezhitsa I AUID- ORCID: 0000-0002-2852-8486 AD - a Centre For Neuroscience Research, Faculty of Medicine , Universiti Teknologi MARA, Sungai Buloh Campus, Selangor , Malaysia. AD - b Research Institute of Pharmacology, Volgograd State Medical University , Volgograd , Russia. FAU - Agarwal, Renu AU - Agarwal R AUID- ORCID: 0000-0002-3050-7449 AD - a Centre For Neuroscience Research, Faculty of Medicine , Universiti Teknologi MARA, Sungai Buloh Campus, Selangor , Malaysia. FAU - Bakar, Nor Salmah AU - Bakar NS AD - a Centre For Neuroscience Research, Faculty of Medicine , Universiti Teknologi MARA, Sungai Buloh Campus, Selangor , Malaysia. FAU - Agarwal, Puneet AU - Agarwal P AD - c IMU Clinical School, International Medical University , Seremban , Malaysia. FAU - Mohd Ismail, Nafeeza AU - Mohd Ismail N AD - a Centre For Neuroscience Research, Faculty of Medicine , Universiti Teknologi MARA, Sungai Buloh Campus, Selangor , Malaysia. LA - eng PT - Journal Article DEP - 20180320 PL - England TA - Int J Neurosci JT - The International journal of neuroscience JID - 0270707 RN - 0 (Amyloid beta-Peptides) RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Peptide Fragments) RN - 0 (amyloid beta-protein (1-40)) SB - IM MH - Amyloid beta-Peptides/administration & dosage/*toxicity MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - In Situ Nick-End Labeling MH - *Optic Nerve/drug effects/metabolism/pathology MH - Oxidative Stress/*drug effects MH - Peptide Fragments/administration & dosage/*toxicity MH - Rats MH - Rats, Sprague-Dawley MH - *Retina/drug effects/metabolism/pathology MH - Vitreous Body/drug effects OTO - NOTNLM OT - Amyloid-beta 1-40 peptide OT - hematoxylin-eosin staining OT - neurotoxicity OT - optic nerve OT - retina OT - toluidine blue staining OT - tunnel staining EDAT- 2018/03/01 06:00 MHDA- 2018/12/24 06:00 CRDT- 2018/03/01 06:00 PHST- 2018/03/01 06:00 [pubmed] PHST- 2018/12/24 06:00 [medline] PHST- 2018/03/01 06:00 [entrez] AID - 10.1080/00207454.2018.1446953 [doi] PST - ppublish SO - Int J Neurosci. 2018 Oct;128(10):952-965. doi: 10.1080/00207454.2018.1446953. Epub 2018 Mar 20.