File Download
Supplementary

postgraduate thesis: The role of electrical stimulation in ophthalmic disorders

TitleThe role of electrical stimulation in ophthalmic disorders
Authors
Issue Date2016
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Fu, L. [傅林]. (2016). The role of electrical stimulation in ophthalmic disorders. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR.
AbstractElectrical stimulation therapy, using low-intensity electrical current, is a novel adjuvant therapeutic technique employed in neurodegenerative diseases, including those of the peripheral nervous system, musculoskeletal system, central nervous system as well as in otorhinolaryngology. Recently electrical stimulation therapy has been shown to protect retinal ganglion cells (RGCs) and retinal photoreceptors from secondary degeneration and preserve retinal function in animals and in-vitro models of end-stage ocular diseases. A better understanding of the underlying mechanism to facilitate the application of this treatment in ocular disease especially irreversible visual defect like glaucoma and aging related maculopathy. For my thesis work, I investigated the potential neuroprotective effects of transcorneal electrical stimulation (TcES) in an animal model of acute ocular hypertensive injury as well as the effect of the electrical current on a photoreceptor cell line exposed to hypoxic injury. During the process, I experimented with different rodents, different methods of intraocular pressure elevation in animals and compared electroretinographic responses in animals of different ages to find the optimum model for my work. For the animal study, acute ocular hypertensive injury was induced in the right eye of all gerbils. They were then divided equally into treatment and sham-treatment groups. In the treatment group, TcES was performed to the surgical eye immediately and twice weekly after AOH for 1 week and 1 month respectively. In the sham treatment group, sham TcES was given to the surgical eye at the same time points. TcES treated eyes had significantly higher RGCs survival rate at 1 month compared to the ones received sham treatments. This was associated with improved RGCs function and vision-related behavior. Furthermore TcES treated eyes were shown to have increased IL-10 protein secretion, with a corresponding reduction in IL-6 and COX-2 secretions as well as reduction in NF-kB phosphorylation when assessed by western blot. This was associated with the suppression of microglial cell activation in TcES treated eyes. I conducted an in vitro study to further investigate the potential molecular mechanisms of TcES induced retinal neuroprotection. Chemical hypoxia was induced in separate photoreceptor cell lines and Müller cell lines using cobalt chloride (II) (CoCl2). Electrical stimulation was then applied to the Müller cell line for 1 hour and the conditional medium was collected 3 and 24 h after stimulation. This conditional medium was then added to the hypoxic photoreceptor cell line for 3 and 24 h accordingly. Cell viability of the 661W was then measured and compared by MTS cell proliferation assay. This model however did not demonstrate any significant improvement in photoreceptor cell survival after exposure to the electrical current treated Müller cell-medium. In conclusion, my thesis work demonstrated that TcES treatment successfully rescued RGCs from secondary degeneration after acute ocular hypertensive injury. My work further suggested that the underlying mechanism involved suppression of microglia activation and inhibition of the NFκB signaling pathway resulting in modulation of the local inflammatory response.
DegreeDoctor of Philosophy
SubjectEye - Diseases - Treatment
Dept/ProgramOphthalmology
Persistent Identifierhttp://hdl.handle.net/10722/240681
HKU Library Item IDb5854996

 

DC FieldValueLanguage
dc.contributor.authorFu, Lin-
dc.contributor.author傅林-
dc.date.accessioned2017-05-09T23:14:55Z-
dc.date.available2017-05-09T23:14:55Z-
dc.date.issued2016-
dc.identifier.citationFu, L. [傅林]. (2016). The role of electrical stimulation in ophthalmic disorders. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR.-
dc.identifier.urihttp://hdl.handle.net/10722/240681-
dc.description.abstractElectrical stimulation therapy, using low-intensity electrical current, is a novel adjuvant therapeutic technique employed in neurodegenerative diseases, including those of the peripheral nervous system, musculoskeletal system, central nervous system as well as in otorhinolaryngology. Recently electrical stimulation therapy has been shown to protect retinal ganglion cells (RGCs) and retinal photoreceptors from secondary degeneration and preserve retinal function in animals and in-vitro models of end-stage ocular diseases. A better understanding of the underlying mechanism to facilitate the application of this treatment in ocular disease especially irreversible visual defect like glaucoma and aging related maculopathy. For my thesis work, I investigated the potential neuroprotective effects of transcorneal electrical stimulation (TcES) in an animal model of acute ocular hypertensive injury as well as the effect of the electrical current on a photoreceptor cell line exposed to hypoxic injury. During the process, I experimented with different rodents, different methods of intraocular pressure elevation in animals and compared electroretinographic responses in animals of different ages to find the optimum model for my work. For the animal study, acute ocular hypertensive injury was induced in the right eye of all gerbils. They were then divided equally into treatment and sham-treatment groups. In the treatment group, TcES was performed to the surgical eye immediately and twice weekly after AOH for 1 week and 1 month respectively. In the sham treatment group, sham TcES was given to the surgical eye at the same time points. TcES treated eyes had significantly higher RGCs survival rate at 1 month compared to the ones received sham treatments. This was associated with improved RGCs function and vision-related behavior. Furthermore TcES treated eyes were shown to have increased IL-10 protein secretion, with a corresponding reduction in IL-6 and COX-2 secretions as well as reduction in NF-kB phosphorylation when assessed by western blot. This was associated with the suppression of microglial cell activation in TcES treated eyes. I conducted an in vitro study to further investigate the potential molecular mechanisms of TcES induced retinal neuroprotection. Chemical hypoxia was induced in separate photoreceptor cell lines and Müller cell lines using cobalt chloride (II) (CoCl2). Electrical stimulation was then applied to the Müller cell line for 1 hour and the conditional medium was collected 3 and 24 h after stimulation. This conditional medium was then added to the hypoxic photoreceptor cell line for 3 and 24 h accordingly. Cell viability of the 661W was then measured and compared by MTS cell proliferation assay. This model however did not demonstrate any significant improvement in photoreceptor cell survival after exposure to the electrical current treated Müller cell-medium. In conclusion, my thesis work demonstrated that TcES treatment successfully rescued RGCs from secondary degeneration after acute ocular hypertensive injury. My work further suggested that the underlying mechanism involved suppression of microglia activation and inhibition of the NFκB signaling pathway resulting in modulation of the local inflammatory response.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshEye - Diseases - Treatment-
dc.titleThe role of electrical stimulation in ophthalmic disorders-
dc.typePG_Thesis-
dc.identifier.hkulb5854996-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineOphthalmology-
dc.description.naturepublished_or_final_version-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats