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postgraduate thesis: Characterization of NG2+ macrophage in glaucoma : an investigation focusing on its origin and potential roles in ischemic retina

TitleCharacterization of NG2+ macrophage in glaucoma : an investigation focusing on its origin and potential roles in ischemic retina
Authors
Advisors
Advisor(s):So, KFChung, SK
Issue Date2014
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Feng, Q. [馮茜]. (2014). Characterization of NG2+ macrophage in glaucoma : an investigation focusing on its origin and potential roles in ischemic retina. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5185941
AbstractMacrophage manipulation as immunomodulatory intervention in glaucoma, a leading cause to blindness characterized by retinal ganglion cell (RGC) loss, has been proposed as a promising strategy to protect RGCs from dying. Three types of macrophage in damaged retinas, microglia-derived macrophage, monocyte-derived macrophage and perivascular macrophage, together consist a highly heterogeneous population with both beneficial and detrimental functions partly resulted from their distinct origins. NG2 (Nerve/glial antigen 2) positive macrophage, a subtype of macrophage, has been considered to fulfill specific functions with neuroprotective and neurogenic potentials. Whether NG2+ macrophage can be a possible target for treatment in glaucoma is unknown. Basic information of this subtype of macrophage in ischemic retinas of a mouse glaucomatous model called acute ocular hypertension (AOH) model was obtained in this study to answer three questions. First, do NG2+ macrophage exist in mouse retina, if so, what do they like? In normal mouse retinas, NG2+ macrophage did not exist. After AOH, NG2 could be induced on macrophage. And they are unevenly distributed in the whole retina while reside in the ganglion cell layer, inner plexiform layer or inner nuclear layer. Moreover, NG2+ macrophage all contained two nuclei with typical amoeboid-like morphologies of macrophage in activation state except the rounded type. Secondly, are they associated with the surrounding cells, if so, how? Close association of RGCs and Müller cells with NG2+ macrophage was found due to their co-localization. To know how they functioned, potential roles regarding its proliferating and phagocytic abilities were revealed by its co-localization with proliferating and phagocytic markers. However, unlike NG2+ macrophage in ischemic brain, NG2+ macrophage in ischemic retina did not express neurotrophic factors while some of them were found to express interlukin-10, an anti-inflammatory cytokine. Possible neurogenic potential was also observed by its co-localization with Nestin, a neural stem cell marker. Thirdly, where do they come from? To know their origins, bone marrow chimeras combined with specific markers were used to distinguish microglia-derived macrophage, monocyte-derived macrophage and perivascular macrophage. And it was found that majority of NG2+ macrophage was originated from resident microglia, rather than monocyte-derived macrophage or perivascular macrophage. Taken together, the present study showed the basic profile of a subtype of macrophage in a mouse model of glaucoma, more accurately, NG2+ macrophage in AOH mouse retinas. NG2 expression was induced mostly in resident microglia in AOH retina as a proliferating population with phagocytic, anti-inflammatory functions, and possible neurogenic potentials. Therefore, NG2+ macrophage may be a potential candidate target for treatment of glaucoma.
DegreeDoctor of Philosophy
SubjectGlaucoma
Macrophages
Dept/ProgramAnatomy
Persistent Identifierhttp://hdl.handle.net/10722/197102

 

DC FieldValueLanguage
dc.contributor.advisorSo, KF-
dc.contributor.advisorChung, SK-
dc.contributor.authorFeng, Qian-
dc.contributor.author馮茜-
dc.date.accessioned2014-05-07T23:15:27Z-
dc.date.available2014-05-07T23:15:27Z-
dc.date.issued2014-
dc.identifier.citationFeng, Q. [馮茜]. (2014). Characterization of NG2+ macrophage in glaucoma : an investigation focusing on its origin and potential roles in ischemic retina. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5185941-
dc.identifier.urihttp://hdl.handle.net/10722/197102-
dc.description.abstractMacrophage manipulation as immunomodulatory intervention in glaucoma, a leading cause to blindness characterized by retinal ganglion cell (RGC) loss, has been proposed as a promising strategy to protect RGCs from dying. Three types of macrophage in damaged retinas, microglia-derived macrophage, monocyte-derived macrophage and perivascular macrophage, together consist a highly heterogeneous population with both beneficial and detrimental functions partly resulted from their distinct origins. NG2 (Nerve/glial antigen 2) positive macrophage, a subtype of macrophage, has been considered to fulfill specific functions with neuroprotective and neurogenic potentials. Whether NG2+ macrophage can be a possible target for treatment in glaucoma is unknown. Basic information of this subtype of macrophage in ischemic retinas of a mouse glaucomatous model called acute ocular hypertension (AOH) model was obtained in this study to answer three questions. First, do NG2+ macrophage exist in mouse retina, if so, what do they like? In normal mouse retinas, NG2+ macrophage did not exist. After AOH, NG2 could be induced on macrophage. And they are unevenly distributed in the whole retina while reside in the ganglion cell layer, inner plexiform layer or inner nuclear layer. Moreover, NG2+ macrophage all contained two nuclei with typical amoeboid-like morphologies of macrophage in activation state except the rounded type. Secondly, are they associated with the surrounding cells, if so, how? Close association of RGCs and Müller cells with NG2+ macrophage was found due to their co-localization. To know how they functioned, potential roles regarding its proliferating and phagocytic abilities were revealed by its co-localization with proliferating and phagocytic markers. However, unlike NG2+ macrophage in ischemic brain, NG2+ macrophage in ischemic retina did not express neurotrophic factors while some of them were found to express interlukin-10, an anti-inflammatory cytokine. Possible neurogenic potential was also observed by its co-localization with Nestin, a neural stem cell marker. Thirdly, where do they come from? To know their origins, bone marrow chimeras combined with specific markers were used to distinguish microglia-derived macrophage, monocyte-derived macrophage and perivascular macrophage. And it was found that majority of NG2+ macrophage was originated from resident microglia, rather than monocyte-derived macrophage or perivascular macrophage. Taken together, the present study showed the basic profile of a subtype of macrophage in a mouse model of glaucoma, more accurately, NG2+ macrophage in AOH mouse retinas. NG2 expression was induced mostly in resident microglia in AOH retina as a proliferating population with phagocytic, anti-inflammatory functions, and possible neurogenic potentials. Therefore, NG2+ macrophage may be a potential candidate target for treatment of glaucoma.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshGlaucoma-
dc.subject.lcshMacrophages-
dc.titleCharacterization of NG2+ macrophage in glaucoma : an investigation focusing on its origin and potential roles in ischemic retina-
dc.typePG_Thesis-
dc.identifier.hkulb5185941-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineAnatomy-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5185941-

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