Increased diabetic retinal neuronal degeneration in IL-33-/- mice is related to reduced Müller cell-derived neurotrophic factors

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Abstract

Purpose : Müller cell activation and malfunction play a critical role in the neural and vascular pathology associated with diabetic retinopathy (DR). IL-33, a member of the IL-1 cytokine family, has diverse roles in inflammatory response and is exclusively expressed in the nuclei of Müller cells in the retina. This study investigated the role of IL-33 in DR with emphasis on diabetic retinal neuronal degeneration.


Methods : Diabetes was induced in wild-type (WT) C57BL/6J and IL-33-/- mice by intraperitoneal injection of streptozotocin. After 6 months diabetes duration, electroretinography (ERG), fundus imaging and optic coherence tomography (OCT) were conducted. DR-related neuronal degeneration was examined by immunohistochemistry. Müller cells from WT and IL-33-/- mice were cultured under normal glucose (5mM) and high glucose (25mM) conditions, and the expression of neurotrophic factors were investigated by real-time RT-PCR and western blotting.


Results : The a- and b-wave amplitude was significantly lower in ERG, and the retinal neurons were significantly thinner in OCT in diabetic IL-33-/- mice when compared to diabetic WT mice. Immunohistochemistry revealed severe photoreceptor degeneration in diabetic IL-33-/- mice compared to diabetic WT mice. Müller cells from IL-33-/- mice expressed significant lower levels of neurotrophic growth factors including CNTF, BDNF, NTF3 and LIF compared to the cells from WT mice (p<0.05). The expression of these neurotrophic growth factors was significantly increased in Müller cells from WT mice following high glucose treatment, but the treatment failed to upregulate the expression of these neurotrophic factors in Müller cells from IL-33-/- mice.


Conclusions : Our results show that neural pathophysiology is increased in the retina of diabetic IL-33-/- mice, which may be related to lower levels neurotrophic factor expression by Müller cells. Also IL-33 may critically control the expression of neurotrophic factors in Müller cells, particularly under stress conditions such as in diabetes.
Original languageEnglish
Publication statusPublished - 2018
EventARVO (The Association for Research in Vision and Ophthalmology ) 2018 Annual Meeting - Hawaii, United States
Duration: 29 Apr 201803 May 2018

Conference

ConferenceARVO (The Association for Research in Vision and Ophthalmology ) 2018 Annual Meeting
CountryUnited States
CityHawaii
Period29/04/201803/05/2018

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