Granzyme B degrades extracellular matrix and promotes inflammation and choroidal neovascularization.

Age-related macular degeneration (AMD) is a common retinal neurodegenerative disease among the elderly. Neovascular AMD (nAMD), a leading cause of AMD-related blindness, involves choroidal neovascularization (CNV), which can be suppressed by anti-angiogenic treatments. However, current CNV treatments do not work in all nAMD patients.

Ergothioneine, a dietary antioxidant improves amyloid beta clearance in the neuroretina of a mouse model of Alzheimer's disease.

Introduction: Ergothioneine (Ergo) is a naturally occurring dietary antioxidant. Ergo uptake is dependent on the transporter, organic cation transporter novel-type 1 (OCTN1) distribution. OCTN1 is highly expressed in blood cells (myeloid lineage cells), brain and ocular tissues that are likely predisposed to oxidative stress.

Granzyme B Contributes to Choroidal Neovascularization and Age-Related Macular Degeneration Through Proteolysis of Thrombospondin-1.

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly. The pathology of neovascular age-related macular degeneration (nAMD), also known as wet AMD, is associated with an abnormal blood vessel growth in the eye and involves an imbalance of proangiogenic and antiangiogenic factors. Thrombospondin (TSP)-1 and TSP-2 are endogenous matricellular proteins that inhibit angiogenesis.

Müller cell degeneration and microglial dysfunction in the Alzheimer's retina.

Amyloid beta (Aβ) deposits in the retina of the Alzheimer's disease (AD) eye may provide a useful diagnostic biomarker for AD. This study focused on the relationship of Aβ with macroglia and microglia, as these glial cells are hypothesized to play important roles in homeostasis and clearance of Aβ in the AD retina. Significantly higher Aβ load was found in AD compared to controls, and specifically in the mid-peripheral region.

Inhalable Thioflavin S for the Detection of Amyloid Beta Deposits in the Retina.

We present an integrated delivery technology herein employing the aerosolized method to repurpose thioflavin S for imaging amyloid beta (Abeta) deposits in the retina as a surrogate of Abeta in the brain for early detection of Alzheimer's disease. The data showed that wild type (WT) mice also have Abeta deposits in the retinae, albeit much less than 5XFAD mice. Further, only in 5XFAD mice, significant Abeta deposits were found associated with retinal ganglion cells (RGCs) in whole-mount and cross-section data.

Amyloid Beta Immunoreactivity in the Retinal Ganglion Cell Layer of the Alzheimer's Eye.

Alzheimer's disease (AD) is the most prevalent form of dementia, accounting for 60-70% of all dementias. AD is often under-diagnosed and recognized only at a later, more advanced stage, and this delay in diagnosis has been suggested as a contributing factor in the numerous unsuccessful AD treatment trials. Although there is no known cure for AD, early diagnosis is important for disease management and care.

Retinal Fluorescence Imaging With Curcumin in an Alzheimer Mouse Model.

Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) plaques in the brain detectable by highly invasive brain imaging or in post-mortem tissues. A non-invasive and inexpensive screening method is needed for early diagnosis of asymptomatic AD patients. The shared developmental origin and similarities with the brain make the retina a suitable surrogate tissue to assess Aβ load in AD.

Evidence for the activation of pyroptotic and apoptotic pathways in RPE cells associated with NLRP3 inflammasome in the rodent eye.

Background: Age-related macular degeneration (AMD) is a devastating eye disease causing irreversible vision loss in the elderly. Retinal pigment epithelium (RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell death in the late stages of the disease. However, the exact mechanisms for RPE degeneration in AMD are still unresolved.

LAMELLAR HOLE-ASSOCIATED EPIRETINAL PROLIFERATION: A Clinicopathologic Correlation.

Purpose: To correlate clinical and optical coherence tomographic features with histopathological and immunohistochemical findings in an eye undergoing surgical excision of lamellar hole-associated epiretinal proliferation (LHEP).

Methods: An eye with a lamellar macular hole and LHEP without a tractional epiretinal membrane component was identified with spectral-domain optical coherence tomographic imaging and underwent pars plana vitrectomy with LHEP and internal limiting membrane peeling and gas tamponade. The surgically excised LHEP specimen was analyzed with histopathological and immunohistochemical staining using flat-mount preparation techniques.

Age-related increases in amyloid beta and membrane attack complex: evidence of inflammasome activation in the rodent eye.

Background: The membrane attack complex (MAC) is a key player in the pathogenesis of age-related macular degeneration (AMD) and is a putative activator of the NLRP3 inflammasome. Amyloid beta (Aβ), a component of drusen deposits, has also been implicated in inflammasome activation by our work and those of others. However, the interactions of MAC and Aβ are still poorly understood, especially their roles in aging and retinal degenerative pathologies.

CFH Y402H polymorphism is associated with elevated vitreal GM-CSF and choroidal macrophages in the postmortem human eye.

Purpose: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in people 50 years of age or older in developed countries. The homozygous CC genotype in the complement factor H (CFH) Y402H single nucleotide polymorphism (SNP; rs1061170) is widely recognized as a risk factor for the development of AMD. In this study, we examined vitreal levels of granulocyte macrophage colony-stimulating factor (GM-CSF), a hematopoietic cytokine, and macrophages in the choroid of postmortem human eyes genotyped for the CFH Y402H SNP.

NLRP3 inflammasome: activation and regulation in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE) and Bruch's membrane (BM) in outer retina.

Vinpocetine inhibits amyloid-beta induced activation of NF-κB, NLRP3 inflammasome and cytokine production in retinal pigment epithelial cells.

Chronic inflammation is a key pathogenic process in age-related macular degeneration (AMD). Amyloid-beta (Aβ) is a constituent of AMD drusen and promotes the activation of NLRP3 inflammasome which facilitates the production of cytokines. We investigated the role of transcription factor NF-κB in the activation of inflammasome in the RPE and the effect of vinpocetine, a dietary supplement with inhibitory effect on NF-κΒ.

Astrocyte and microglial activation in the lateral geniculate nucleus and visual cortex of glaucomatous and optic nerve transected primates.

Purpose: To examine early cellular changes, including astrocyte reactivity and microglial activation, in the central nervous system (CNS) after unilateral optic nerve transection (ONT) or ocular hypertension (OHT) in monkeys.

Methods: Unilateral ONT or OHT was achieved in monkeys for periods ranging from two weeks to two months in duration. After intracardial perfusion, sections of the lateral geniculate nucleus (LGN) and visual cortex (V1) were examined by immunohistochemistry for glial fibrillary acidic protein (GFAP) and CD11b, a subunit of the complement 3 receptor and marker of macrophage and microglia cells (MAC-1).

Amyloid-beta deposits lead to retinal degeneration in a mouse model of Alzheimer disease.

Purpose: To compare the temporal and spatial expression patterns of amyloid precursor protein (APP), amyloid-beta deposits, inflammatory chemokines, and apoptosis in the retina of a mouse model of Alzheimer disease (AD).

Methods: Retinas of transgenic mice harboring a mutant presenilin (PS1) and a mutant APP gene were processed for TUNEL and immunohistochemistry with antibodies against APP, amyloid-beta, monocyte chemotactic protein (MCP)-1, and F4/80. Comparisons were made between age groups and between transgenic and wild-type congeners.

Complement-associated deposits in the human retina.

Purpose: The purpose of this study was to investigate complement activation and associated inflammatory mechanisms in normal, aged human retina.

Methods: Evidence of complement activation and associated mechanisms was assessed in normal human retina (n = 52) using a panel of antibodies directed against membrane attack complex (C5b-9), microglia (CD11b), amyloid precursor protein (APP), scavenger receptor (CD36), and a phytolectin (RCA-I). Fifty-two eyes, categorized into two age groups, were used.

Neurochemical correlates of cortical plasticity after unilateral elevated intraocular pressure in a primate model of glaucoma.

Purpose: To examine the time course of changes in the expression patterns of several synaptic plasticity markers in the primary visual cortex after unilateral elevated intraocular pressure (IOP) in a primate model of glaucoma.

Methods: A monkey model of experimental glaucoma was combined with immunohistochemical and histochemical methods to assess changes in expression patterns and metabolic activity of cortical neurons in V1.

Results: Experimental unilateral glaucoma altered the spatial and temporal distribution of several neurochemicals associated with cortical plasticity in V1 of the primate.

Expression of neuropilin-1 in choroidal neovascular membranes.

Background: Neovascularization is a serious consequence of several eye diseases, including age-related macular degeneration. Neovascularization is under the control of proangiogenic factors, such as vascular endothelial growth factor and fibroblast growth factor. Recent work in our laboratory has focused on other, novel angiogenic factors, such as neuropilin-1, and their potential role in neovascularization.