Retinal Degeneration and Alzheimer’s Disease: An Evolving Link

Ashok, Ajay; Singh, Neena; Chaudhary, Suman; Bellamkonda, Vindhya; Kritikos, Alexander E; Wise, Aaron; Rana, Neil; McDonald, Dallas; Ayyagari, Rithvik

doi:10.3390/ijms21197290

Cited by 105 publications

(80 citation statements)

References 155 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Calpain-1 is involved in the cleavage of tau protein at multiple sites that contribute to both clearance and accumulation of fibril formation [ 35 ]. Intriguingly, Alzheimer's disease is often associated with age-related macular degeneration and glaucoma, and common features including amyloid β plaque deposition, chronic inflammation, iron accumulation, and oxidative stress have been reported [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Calpain-1 C2L domain peptide protects mouse hippocampus-derived neuronal HT22 cells against glutamate-induced oxytosis

Sugawara

Abe²,

Kasai³

et al. 2021

Biochemistry and Biophysics Reports

View full text Add to dashboard Cite

Calpains are Ca 2+ -dependent cysteine proteases; their aberrant activation is associated with several neurodegenerative diseases. The μ-calpain catalytic subunit, calpain-1, is located in the cytoplasm as well as in the mitochondria. Mitochondrial calpain-1 cleaves apoptosis-inducing factor (AIF), leading to apoptotic cell death. We have previously reported that short peptides of calpain-1 C2-like domain conjugated with cell penetrating peptide HIV-Tat (Tat-μCL) selectively inhibit mitochondrial calpain-1 and effectively prevent neurodegenerative diseases of the eye. In this study, we determined whether mitochondrial calpain-1 mediates oxytosis (oxidative glutamate toxicity) in hippocampal HT22 cells using Tat-μCL and newly generated polyhistidine-conjugated μCL peptide and compared their efficacies in preventing oxytosis. TUNEL assay and single strand DNA staining revealed that both μCL peptides inhibited glutamate-induced oxytosis. Additionally, both the peptides suppressed the mitochondrial AIF translocation into the nucleus. All polyhistidine-μCL peptides (containing 4–16 histidine residues) showed higher cell permeability than Tat-μCL. Notably, tetrahistidine (H4)-μCL exerted the highest cytoprotective activity. Thus, H4-μCL may be a potential peptide drug for calpain-1-mediated neurodegenerative diseases such as Alzheimer's disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Calpain-1 C2L domain peptide protects mouse hippocampus-derived neuronal HT22 cells against glutamate-induced oxytosis

Sugawara

Abe²,

Kasai³

et al. 2021

Biochemistry and Biophysics Reports

View full text Add to dashboard Cite

show abstract

“…The hallmark pathology of AMD is ocular drusen and extracellular deposits located between the retinal pigment epithelium (RPE) and Bruch's membrane [12]. Similar to senile plaques in AD, Aβ is also an important constituent in drusen [13][14][15]. Previous study has demonstrated that the Aβ in drusen correlates with the location of photoreceptors and RPE cell degeneration [16].…”

Section: Introductionmentioning

confidence: 99%

Increased risk of Alzheimer’s disease among patients with age-related macular degeneration: A nationwide population-based study

et al. 2021

View full text Add to dashboard Cite

Objective This study aimed to investigate the risk of Alzheimer’s disease among patients with age-related macular degeneration and its association with confounding comorbidities. Method This was a population-based, retrospective cohort study. By accessing data from the National Health Insurance Research Database of Taiwan, we identified 10,578 patients aged 50–100 years who were newly diagnosed with age-related macular degeneration between 2000 and 2012 and 10,578 non- age-related macular degeneration individuals. The comorbidities assessed were osteoporosis, diabetes, cirrhosis, cerebrovascular disease, chronic kidney disease, hypertension, hyperlipidemia, coronary artery disease, and chronic obstructive pulmonary disease. Results Patients with age-related macular degeneration had a 1.23-fold increased risk of their condition advancing to Alzheimer’s disease (aHR = 1.23, 95% CI = 1.04–1.46). The younger patients were diagnosed with age-related macular degeneration, the more likely patients got Alzheimer’s disease (50–64 age group: aHR = 1.97, 95% CI = 1.04–3.73; 65–79 age group: aHR = 1.27, 95% CI = 1.02–1.58; 80–100 age group: aHR = 1.06, 95% CI = 0.78–1.45). In addition, there were significantly higher risks of Alzheimer’s disease for patients with cirrhosis (aHR = 1.50, 95% CI = 1.09–2.06) in the age-related macular degeneration cohort than in the non-age-related macular degeneration cohort. Conclusion Patients with age-related macular degeneration may exhibit a higher risk of Alzheimer’s disease than people without age-related macular degeneration.

show abstract

“…Prion and “prion-like” diseases are known to cause retinal damage in humans and other species, but each disease affects the retina in unique ways [ 44 ]. In Alzheimer’s disease patients, Aβ deposition has been associated with degeneration of the retinal ganglion cell layer, photoreceptors and the retinal pigmented epithelium [ 3 , 45 ]. Ratnayaka et al have also shown that Aβ plaques may be a key factor in Age-related Macular Degeneration (AMD).…”

Section: Introductionmentioning

confidence: 99%

Prion-induced photoreceptor degeneration begins with misfolded prion protein accumulation in cones at two distinct sites: cilia and ribbon synapses

Striebel

Race

Leung

et al. 2021

acta neuropathol commun

View full text Add to dashboard Cite

Accumulation of misfolded host proteins is central to neuropathogenesis of numerous human brain diseases including prion and prion-like diseases. Neurons of retina are also affected by these diseases. Previously, our group and others found that prion-induced retinal damage to photoreceptor cells in mice and humans resembled pathology of human retinitis pigmentosa caused by mutations in retinal proteins. Here, using confocal, epifluorescent and electron microscopy we followed deposition of disease-associated prion protein (PrPSc) and its association with damage to critical retinal structures following intracerebral prion inoculation. The earliest time and place of retinal PrPSc deposition was 67 days post-inoculation (dpi) on the inner segment (IS) of cone photoreceptors. At 104 and 118 dpi, PrPSc was associated with the base of cilia and swollen cone inner segments, suggesting ciliopathy as a pathogenic mechanism. By 118 dpi, PrPSc was deposited in both rods and cones which showed rootlet damage in the IS, and photoreceptor cell death was indicated by thinning of the outer nuclear layer. In the outer plexiform layer (OPL) in uninfected mice, normal host PrP (PrPC) was mainly associated with cone bipolar cell processes, but in infected mice, at 118 dpi, PrPSc was detected on cone and rod bipolar cell dendrites extending into ribbon synapses. Loss of ribbon synapses in cone pedicles and rod spherules in the OPL was observed to precede destruction of most rods and cones over the next 2–3 weeks. However, bipolar cells and horizontal cells were less damaged, indicating high selectivity among neurons for injury by prions. PrPSc deposition in cone and rod inner segments and on the bipolar cell processes participating in ribbon synapses appear to be critical early events leading to damage and death of photoreceptors after prion infection. These mechanisms may also occur in human retinitis pigmentosa and prion-like diseases, such as AD.

show abstract

Retinal Degeneration and Alzheimer’s Disease: An Evolving Link

Cited by 105 publications

References 155 publications

Calpain-1 C2L domain peptide protects mouse hippocampus-derived neuronal HT22 cells against glutamate-induced oxytosis

Calpain-1 C2L domain peptide protects mouse hippocampus-derived neuronal HT22 cells against glutamate-induced oxytosis

Increased risk of Alzheimer’s disease among patients with age-related macular degeneration: A nationwide population-based study

Prion-induced photoreceptor degeneration begins with misfolded prion protein accumulation in cones at two distinct sites: cilia and ribbon synapses

Contact Info

Product

Resources

About