<i>β</i>-actin is essential for structural integrity and physiological function of the retina

Vedula, Pavan; Fina, Marie E.; Bell, Brent A.; Nikonov, Sergei; Kashina, Anna; Dong, Dawei

doi:10.1101/2023.03.27.534392

Cited by 3 publications

(1 citation statement)

References 69 publications

(121 reference statements)

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“…It appears that the β-actin labeling is specific to cones, but this cannot be confirmed. The role of β-actin in the structural integrity and physiological function of the RPE and photoreceptors is an active area of research ( 74 ). Collectively, these experiments demonstrate the identification and localization of the α7 nAChR to potential therapeutic targets in the mammalian retina.…”

Section: Resultsmentioning

confidence: 99%

Target identification and validation of the alpha7 nicotinic acetylcholine receptor as a potential therapeutic target in retinal disease

Linn¹

2023

Front. Ophthalmol.

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The role of acetylcholine (ACh) in visual processing in the mammalian retina has been the focus of research for many decades. Pioneering work on the localization of ACh discovered that the neurotransmitter is synthesized and stored in a distinct subpopulation of amacrine (starburst) cells. It has been shown that ACh release is regulated to a low resting “tonic” level, much like what is observed at the neuromuscular junction (NMJ). If there were a dysfunction in the tonic release of ACh, might post-synaptic changes render the targets of ACh [i.e., retinal ganglion cells (RGCs)] vulnerable to disease? During my time at Pharmacia & Upjohn (PNU), selective nicotinic ACh receptor (nAChR) agonists (e.g., PNU-282987) were developed as a possible therapy for central nervous system (CNS) diseases. As RGCs are the main targets of neurodegeneration in glaucoma, could the activation of this target provide neuroprotection? In response to this question, experiments to identify alpha7 nAChRs in the retina (i.e., target ID studies) followed by “proof-of-concept” experiments were conducted. Target ID studies included binding studies with retinal homogenates, [125I]-alpha-bungarotoxin (α-BTX) autoradiography, and fluorescently tagged α-BTX binding in retinal slices. Imaging studies of intracellular calcium dynamics in the retinal slice were conducted. Reverse transcription-polymerase chain reaction (RT-PCR) analysis with alpha7 nAChR knockout mice using the “laser-capture microdissection” technique, in situ hybridization studies, and RT-PCR analysis of the human retina were conducted. Collectively, these experiments confirmed the presence of alpha7 nAChRs on specific cells in the retina. “Proof-of-concept” neuroprotection studies demonstrated that PNU-282987 provided significant protection for RGCs. This protection was dose dependent and was blocked with selective antagonists. More recently, evidence for the generation of new RGCs has been reported with PNU-282987 in rodents. Interestingly, the appearance of new RGCs is more pronounced with eye-drop application than with intravitreal injection. One could postulate that this reflects the neurogenic activation of alpha7 receptors on the retinal pigment epithelium (RPE) (eye drops) vs. a neuroprotective effect on RGCs (injections). In conclusion, there does appear to be a cholinergic retinal “tone” associated with RGCs that could be utilized as a neuroprotective therapy. However, a distinct cholinergic neurogenic mechanism also appears to exist in the outer retina that could possibly be exploited to generate new RGCs lost through various disease processes.

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Section: Resultsmentioning

confidence: 99%

Target identification and validation of the alpha7 nicotinic acetylcholine receptor as a potential therapeutic target in retinal disease

Linn¹

2023

Front. Ophthalmol.

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Structural and functional mechanisms of actin isoforms

Heissler,

Chinthalapudi

2024

The FEBS Journal

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Actin is a highly conserved and fundamental protein in eukaryotes and participates in a broad spectrum of cellular functions. Cells maintain a conserved ratio of actin isoforms, with muscle and non‐muscle actins representing the main actin isoforms in muscle and non‐muscle cells, respectively. Actin isoforms have specific and redundant functional roles and display different biochemistries, cellular localization, and interactions with myosins and actin‐binding proteins. Understanding the specific roles of actin isoforms from the structural and functional perspective is crucial for elucidating the intricacies of cytoskeletal dynamics and regulation and their implications in health and disease. Here, we review how the structure contributes to the functional mechanisms of actin isoforms with a special emphasis on the questions of how post‐translational modifications and disease‐linked mutations affect actin isoforms biochemistry, function, and interaction with actin‐binding proteins and myosin motors.

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PSCA gene expression in bladder, colorectal and prostate cancer patients from Basrah governorate southern of Iraq

Ayoob,

Al-Badran,

Abood

2024

APJMBB

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Cancer causes death in all countries of the world, with approximately (9.6) million deaths in 2018. Developing countries have high cancer rates. Furthermore, there are risk factors that lead to cancer, including economic and political instability and bad lifestyles. This is the first study of PSCA gene expression with BC, CRC and PC in Iraq, especially in Basrah governorate. This paper involved one hundred and one blood samples being collected from bladder, colorectal and prostate cancer. On the other hand, one hundred and one blood samples with no cancer were collected as a control group. Two ml of peripheral blood was drawn for RNA extraction, then total RNA was reverse transcribed to cDNA, and PSCA mRNA was measured using qPCR. The results showed PSCA gene was over expressed in bladder cancer (BC) with an expression level at ± 8.63 for patients and controls estimated with ±4.16. The gene expression was a 2-fold change in patients compared to healthy control. While the PSCA gene was over-expressed in colorectal cancer (CRC) with an expression level ± 8.16 for patients and controls estimated at ±3.30. That means the gene expression was a 2.47-fold change in patients compared to healthy control. The PSCA gene was over expressed in prostate cancer (PC) with an expression level ± 9.47 for patients and controls estimated at ±4.22. The gene expression was a 2.24-fold change in patients compared to healthy control. In the present study, PSCA gene was expressed at a significantly higher level in the BC, CRC and PC patients compared in the controls group.

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β-actin is essential for structural integrity and physiological function of the retina

Cited by 3 publications

References 69 publications

Target identification and validation of the alpha7 nicotinic acetylcholine receptor as a potential therapeutic target in retinal disease

Target identification and validation of the alpha7 nicotinic acetylcholine receptor as a potential therapeutic target in retinal disease

Structural and functional mechanisms of actin isoforms

PSCA gene expression in bladder, colorectal and prostate cancer patients from Basrah governorate southern of Iraq

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