Fluorescence Spectroscopy of the Retina for Diagnosis of Transmissible Spongiform Encephalopathies

Adhikary, Ramkrishna; Mukherjee, Prasun; Krishnamoorthy, G.; Kunkle, Robert A.; Casey, Thomas A.; Rasmussen, Mark A.; Petrich, Jacob W.

doi:10.1021/ac100179u

Cited by 16 publications

(15 citation statements)

References 40 publications

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“…Our results are consistent with the previous reports on fluorescence studies of healthy and scrapie-infected retina of sheep (13). The retinal fluorescence from the scrapie-infected mice showed substantially higher fluorescence and more heterogeneity in the distribution of lipofuscin, compared with retinas of uninfected mice.…”

Section: Discussionsupporting

confidence: 93%

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Fluorescence Spectroscopy of the Retina from Scrapie‐Infected Mice

Bose

Schönenbrücher

Richt

et al. 2013

Photochem & Photobiology

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Recently, we have proposed that the fluorescence spectra of sheep retina can be well correlated with the presence or absence of scrapie. Scrapie is the most widespread TSE (transmissible spongiform encephalopathy) affecting sheep and goats worldwide. Mice eyes have been previously reported as a model system to study age-related accumulation of lipofuscin, which has been investigated by monitoring the increasing fluorescence with age covering its entire life span. The current work aims at developing mice retina as a convenient model system to diagnose scrapie and other fatal TSE diseases in animals such as sheep and cows. The objective of the research reported here was to determine whether the spectral features are conserved between two different species namely mice and sheep, and whether an appropriate small animal model system could be identified for diagnosis of scrapie based on the fluorescence intensity in retina. The results were consistent with the previous reports on fluorescence studies of healthy and scrapie-infected retina of sheep. The fluorescence from the retinas of scrapie-infected sheep was significantly more intense and showed more heterogeneity than that from the retinas of uninfected mice. Although the structural characteristics of fluorescence spectra of scrapie-infected sheep and mice eyes are slightly different, more importantly, murine retinas reflect the enhancement of fluorescence intensity upon infecting the mice with scrapie, which is consistent with the observations in sheep eyes.

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Section: Discussionsupporting

confidence: 93%

“…Recently, we have proposed that the fluorescence spectra of sheep retina can be well correlated with the presence or absence of scrapie . Scrapie is the most widespread TSE affecting sheep and goats worldwide.…”

Section: Introductionmentioning

confidence: 99%

Fluorescence Spectroscopy of the Retina from Scrapie‐Infected Mice

Bose

Schönenbrücher

Richt

et al. 2013

Photochem & Photobiology

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“…MUC1 CT is a trans-membrane receptor that is known to function as an oncoprotein [22–24]. The tyrosines in MUC1 CT are essential for the oncogenic signal to occur in pancreatic cancer cells [14] and contains a YTNP site that, when phosphorylated, interacts with the proteins of the MAPK pathway [10, 11]. Our data and the above findings enable us to postulate that MUC1 contributes to pancreatic cancer cell growth and survival by promoting activation of the MAPK pathway, as pharmaceutically inhibiting this pathways inhibited proliferation in MUC1-expressing cells.…”

Section: Discussionmentioning

confidence: 99%

“…KC mice were generated in our laboratory on the C57BL/6 background by mating the P48-Cre with the LSL-KRAS G12D mice [10–11]. They were further mated to the MUC1.Tg mice to generate KCM mice [3, 12] or to the Muc1KO mice [13] to generate KCKO mice.…”

Section: Methodsmentioning

confidence: 99%

Pancreatic Ductal Adenocarcinoma Mice Lacking Mucin 1 Have a Profound Defect in Tumor Growth and Metastasis

et al. 2011

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MUC1 is over expressed and aberrantly glycosolated in >60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In the present study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared to both KC and KCM. Cell lines derived from KCKO tumors have significantly lower tumorigenic capacity compared to cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared to mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or matrix metalloproteinase-9 (MMP9). Further, significantly fewer KCKO cells entered the G2M phase of the cell cycle compared to the KCM cells. Proteomics and western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of MAPK, as well as a significant decrease in Nestin and Tubulin α-2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse in order to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro.

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“…The retina provides a convenient site to examine loss of function and gain of toxic function by these proteins in vivo during disease progression, and has been used successfully for the early diagnosis of some of these disorders. For example, Optical Coherence Tomography (OCT) is used for the early diagnosis of prion disorders, AD, PD, amyotrophic lateral sclerosis, and multiple sclerosis, to mention a few, and the sensitivity and specificity of the test is improving consistently (Adhikary et al, 2010;Doustar et al, 2017;Torrent et al, 2010). Likewise, retinal function measured by electroretinogram (ERG) is emerging as a sensitive test for retinal function in the early stages of these disorders (Ngoo et al, 2019).…”

Section: The Eye As a 'Window' To The Brainmentioning

confidence: 99%

Prions and prion diseases: Insights from the eye

Singh

Chaudhary

Ashok

et al. 2020

Experimental Eye Research

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Prion diseases are invariably fatal neurodegenerative disorders that have gained much publicity due to their transmissible nature. Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common human prion disorder, with an incidence of 1 in a million. Inherited prion disorders are relatively rare, and associated with mutations in the prion protein gene. More than 50 different point mutations, deletions, and insertions have been identified so far. Most are autosomal dominant and fully penetrant. Prion disorders also occur in animals, and are of major concern because of the potential for spreading to humans. The principal pathogenic event underlying all prion disorders is a change in the conformation of prion protein (PrP C ) from a mainly α-helical to a β-sheet rich isoform, PrP-scrapie (PrP Sc ). Accumulation of PrP Sc in the brain parenchyma is the major cause of neuronal degeneration. The mechanism by which PrP Sc is transmitted, propagates, and causes neurodegenerative changes has been investigated over the years, and several clues have emerged. Efforts are also ongoing for identifying specific and sensitive diagnostic tests for sCJD and animal prion disorders, but success has been limited. The eye is suitable for these evaluations because it shares several anatomical and physiological features with the brain, and can be observed in vivo during disease progression. The retina, considered an extension of the central nervous system, is involved extensively in prion disorders. Accordingly, Optical Coherence Tomography and electroretinogram have shown some promise as pre-mortem diagnostic tests for human and animal prion disorders. However, a complete understanding of the physiology of PrP C and pathobiology of PrP Sc in the eye is essential for developing specific and sensitive tests. Below, we summarize recent progress in ocular physiology and pathology in prion disorders, and the eye as an anatomically accessible site to diagnose, monitor disease progression, and test therapeutic options.

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Fluorescence Spectroscopy of the Retina for Diagnosis of Transmissible Spongiform Encephalopathies

Cited by 16 publications

References 40 publications

Fluorescence Spectroscopy of the Retina from Scrapie‐Infected Mice

Fluorescence Spectroscopy of the Retina from Scrapie‐Infected Mice

Pancreatic Ductal Adenocarcinoma Mice Lacking Mucin 1 Have a Profound Defect in Tumor Growth and Metastasis

Prions and prion diseases: Insights from the eye

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