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Neuroprotective effects of brain-derived neurotrophic factor against amyloid beta 1-40-induced retinal and optic nerve damage

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

Eur J Neurosci, 2020 06;51(12):2394-2411.
PMID: 31883161 DOI: 10.1111/ejn.14662

Brain-derived neurotrophic factor (BDNF) could be considered a potential neuroprotective therapy in amyloid beta (Aβ)-associated retinal and optic nerve degeneration. Hence, in this study we investigated the neuroprotective effect of BDNF against Aβ1-40-induced retinal and optic nerve injury. In this study, exposure to Aβ1-40 was associated with retinal and optic nerve injury. TUNEL staining showed significant reduction in the apoptotic cell count in the BDNF-treated group compared with Aβ1-40 group. H&E-stained retinal sections also showed a striking reduction in neuronal cells in the ganglion cell layer (GCL) of retinas fourteen days after Aβ1-40 exposure. By contrast, number of retinal cells was preserved in the retinas of BDNF-treated animals. After Aβ1-40 exposure, visible axonal swelling was observed in optic nerve sections. However, the BDNF-treated group showed fewer changes in optic nerve; axonal swelling was less frequent and less marked. In the present study, exposure to Aβ was associated with oxidative stress, whereas levels of retinal glutathione (GSH), superoxide dismutase (SOD) and catalase were significantly increased in BDNF-treated than in Aβ1-40-treated rats. Both visual object recognition tests using an open-field arena and a Morris water maze showed that BDNF improved rats' ability to recognise visual cues (objects with different shapes) after Aβ1-40 exposure, thus demonstrating that the visual performance of rats was relatively preserved following BDNF treatment. In conclusion, intravitreal treatment with BDNF prevents Aβ1-40-induced retinal cell apoptosis and axon loss in the optic nerve of rats by reducing retinal oxidative stress and restoring retinal BDNF levels.
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.
Fulltext Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in Glaucoma: A Review of Current State of the Art

Lambuk L, Mohd Lazaldin MA, Ahmad S, Iezhitsa I, Agarwal R, Uskoković V, et al.

Front Pharmacol, 2022;13:875662.
PMID: 35668928 DOI: 10.3389/fphar.2022.875662

Retinal ganglion cells (RGCs) are neurons of the visual system that are responsible for transmitting signals from the retina to the brain via the optic nerve. Glaucoma is an optic neuropathy characterized by apoptotic loss of RGCs and degeneration of optic nerve fibers. Risk factors such as elevated intraocular pressure and vascular dysregulation trigger the injury that culminates in RGC apoptosis. In the event of injury, the survival of RGCs is facilitated by neurotrophic factors (NTFs), the most widely studied of which is brain-derived neurotrophic factor (BDNF). Its production is regulated locally in the retina, but transport of BDNF retrogradely from the brain to retina is also crucial. Not only that the interruption of this retrograde transport has been detected in the early stages of glaucoma, but significantly low levels of BDNF have also been detected in the sera and ocular fluids of glaucoma patients, supporting the notion that neurotrophic deprivation is a likely mechanism of glaucomatous optic neuropathy. Moreover, exogenous NTF including BDNF administration was shown reduce neuronal loss in animal models of various neurodegenerative diseases, indicating the possibility that exogenous BDNF may be a treatment option in glaucoma. Current literature provides an extensive insight not only into the sources, transport, and target sites of BDNF but also the intracellular signaling pathways, other pathways that influence BDNF signaling and a wide range of its functions. In this review, the authors discuss the neuroprotective role of BDNF in promoting the survival of RGCs and its possible application as a therapeutic tool to meet the challenges in glaucoma management. We also highlight the possibility of using BDNF as a biomarker in neurodegenerative disease such as glaucoma. Further we discuss the challenges and future strategies to explore the utility of BDNF in the management of glaucoma.
Fulltext A Comprehensive Review on the Processing of Dried Fish and the Associated Chemical and Nutritional Changes

Fitri N, Chan SXY, Che Lah NH, Jam FA, Misnan NM, Kamal N, et al.

Foods, 2022 Sep 20;11(19).
PMID: 36230013 DOI: 10.3390/foods11192938

Fish is a good source of nutrients, although it is easily spoiled. As such, drying is a common method of preserving fish to compensate for its perishability. Dried fish exists in different cultures with varying types of fish used and drying methods. These delicacies are not only consumed for their convenience and for their health benefits, as discussed in this review. Most commonly, salt and spices are added to dried fish to enhance the flavours and to decrease the water activity (aw) of the fish, which further aids the drying process. For fish to be dried effectively, the temperature, drying environment, and time need to be considered along with the butchering method used on the raw fish prior to drying. Considering the various contributing factors, several physicochemical and biochemical changes will certainly occur in the fish. In this review, the pH, water activity (aw), lipid oxidation, and colour changes in fish drying are discussed as well as the proximate composition of dried fish. With these characteristic changes in dried fish, the sensory, microbial and safety aspects of dried fish are also affected, revolving around the preferences of consumers and their health concerns, especially based on how drying is efficient in eliminating/reducing harmful microbes from the fish. Interestingly, several studies have focused on upscaling the efficiency of dried fish production to generate a safer line of dried fish products with less effort and time. An exploratory approach of the published literature was conducted to achieve the purpose of this review. This evaluation gathers important information from all available library databases from 1990 to 2022. In general, this review will benefit the fishery and food industry by enabling them to enhance the efficiency and safety of fish drying, hence minimising food waste without compromising the quality and nutritional values of dried fish.