Dataset Information

Transcorneal but not transpalpebral electrical stimulation disrupts mucin homeostasis of the ocular surface.

ABSTRACT:

Purpose

Transcorneal electrical stimulation (TcES) is increasingly applied as a therapy for preserving and improving vision in retinal neurodegenerative and ischemic disorders. However, a common complaint about TcES is its induction of eye pain and dryness in the clinic, while the mechanisms remain unknown.

Method

TcES or transpalpebral ES (TpES) was conducted in C57BL6j mice for 14 days. The contralateral eyes were used as non-stimulated controls. Levels of intracellular [Ca²⁺] ([Ca²⁺]_i) were assessed by Fura-2AM. The conductance resistances of the eye under various ES conditions were measured in vivo by an oscilloscope.

Results

Although TcES did not affect tear production, it significantly induced damage to the ocular surface, as revealed by corneal fluorescein staining that was accompanied by significantly decreased mucin (MUC) 4 expression compared to the control. Similar effects of ES were detected in cultured primary corneal epithelium cells, showing decreased MUC4 and ZO-1 levels after the ES in vitro. In addition, TcES decreased secretion of MUC5AC from the conjunctiva in vivo, which was also corroborated in goblet cell cultures, where ES significantly attenuated carbachol-induced [Ca²⁺]_i increase. In contrast to TcES, transpalpebral ES (TpES) did not induce corneal fluorescein staining while significantly increasing tear production. Importantly, the conductive resistance from orbital skin to the TpES was significantly smaller than that from the cornea to the retina in TcES.

Conclusion

TcES, but not TpES, induces corneal epithelial damage in mice by disrupting mucin homeostasis. TpES thus may represent a safer and more effective ES approach for treating retinal neurodegeneration clinically.

SUBMITTER: Yang M

PROVIDER: S-EPMC9756492 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Transcorneal but not transpalpebral electrical stimulation disrupts mucin homeostasis of the ocular surface.

Yang Menglu M Lennikov Anton A Chang Karen K Ashok Ajay A Lee Cherin C Cho Kin-Sang KS Utheim Tor Paaske TP Dartt Darlene A DA Chen Dong Feng DF

BMC ophthalmology 20221215 1

<h4>Purpose</h4>Transcorneal electrical stimulation (TcES) is increasingly applied as a therapy for preserving and improving vision in retinal neurodegenerative and ischemic disorders. However, a common complaint about TcES is its induction of eye pain and dryness in the clinic, while the mechanisms remain unknown.<h4>Method</h4>TcES or transpalpebral ES (TpES) was conducted in C57BL6j mice for 14 days. The contralateral eyes were used as non-stimulated controls. Levels of intracellular [Ca<sup> ...[more]

PMID: 36522696

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Project description:PurposeTranscorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). The aim of our study was to observe changes in optical coherence tomography angiography (OCTA) that would be attributed to TES treatment.MethodsA total of 73 eyes were included: 43 eyes of 22 subjects (11 ♀, 11 ♂) suffering from RP were examined at baseline (BL), after first stimulation (TS), 1 week (1W), and 6 months (6M) after treatment initiation and were compared with 30 control eyes of 15 subjects (8 ♀, 7 ♂). TES was performed simultaneously on both eyes for 30 min weekly. OCTA scans of 9 × 15 mm were recorded with a PLEX Elite 9000 swept-source OCTA device (Carl Zeiss Meditec AG, Jena). Vascular density metrics such as perfusion density (PD) and vessel density (VD) were calculated automatically for the macular area by using standardised extended early treatment diabetic retinopathy study (ETDRS) grids centred around the fovea. In addition, the capillary perfusion density (CPD) and the capillary flux index (CFI) of the peripapillary nerve fibre layer microvasculature in all four quadrants of an annulus centred at the optic disc were measured. All parameters were determined over all retinal layers and separately for the superficial (SCP) and deep capillary plexus (DCP). ANOVA-based linear mixed-effects models were calculated with SPSS®.ResultsThroughout the course of TES treatment, the macular VD and PD of all retinal layers in all subsections showed a slight decrement without reaching statistical significance, also when analysed separately in the SCP and DCP (p > 0.08). In analogy, the average CPD and CFI also presented with a slight decrement (p > 0.20). However, when compared with controls, most OCTA parameters showed a significant decrement (p < 0.05). When analysed systematically in all subsections of the extended ETDRS grid, the temporal macular subsections within the outer ring (radius 1.5-3 mm) and also of the peripheral C1, C2, and C3 rings (radius 3-7.5 mm) showed lower VD and PD values when compared with the other subsections (p < 0.05).ConclusionVascular density metrics in the macular region and the peripapillary microvasculature appear to remain unaffected by continuous TES treatment within a period of 6 months.

Project description:To investigate neuromodulation of functional and directional connectivity features in both visual and non-visual brain cortices after short-term and long-term retinal electrical stimulation in retinal degeneration mice. We performed spontaneous electrocorticography (ECoG) in retinal degeneration (rd) mice following prolonged transcorneal electrical stimulation (pTES) at varying currents (400, 500 and 600 μA) and different time points (transient or day 1 post-stimulation, 1-week post-stimulation and 2-weeks post-stimulation). We also set up a sham control group of rd mice which did not receive any electrical stimulation. Subsequently we analyzed alterations in cross-frequency coupling (CFC), coherence and directional connectivity of the primary visual cortex and the prefrontal cortex. It was observed that the sham control group did not display any significant changes in brain connectivity across all stages of electrical stimulation. For the stimulated groups, we observed that transient electrical stimulation of the retina did not significantly alter brain coherence and connectivity. However, for 1-week post-stimulation, we identified enhanced increase in theta-gamma CFC. Meanwhile, enhanced coherence and directional connectivity appeared predominantly in theta, alpha and beta oscillations. These alterations occurred in both visual and non-visual brain regions and were dependent on the current amplitude of stimulation. Interestingly, 2-weeks post-stimulation demonstrated long-lasting enhancement in network coherence and connectivity patterns at the level of cross-oscillatory interaction, functional connectivity and directional inter-regional communication between the primary visual cortex and prefrontal cortex. Application of electrical stimulation to the retina evidently neuromodulates brain coherence and connectivity of visual and non-visual cortices in retinal degeneration mice and the observed alterations are largely maintained. pTES holds strong possibility of modulating higher cortical functions including pathways of cognition, awareness, emotion and memory.

Dataset Information

Transcorneal but not transpalpebral electrical stimulation disrupts mucin homeostasis of the ocular surface.

Purpose

Method

Results

Conclusion

Publications

Transcorneal but not transpalpebral electrical stimulation disrupts mucin homeostasis of the ocular surface.

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