Pathophysiological Function of Endogenous Calcitonin Gene–Related Peptide in Ocular Vascular Diseases

Toriyama, Yuichi; Iesato, Yasuhiro; Imai, Atsushi; Sakurai, Takayuki; Kamiyoshi, Akiko; Ichikawa-Shindo, Yuka; Kawate, Hisaka; Yamauchi, Akira; Igarashi, Kyoko; Tanaka, Megumu; Tian, Li; Xian, Xian; Zhai, Ling; Owa, Shinji; Murata, Toshinori; Shindo, Takayuki

doi:10.1016/j.ajpath.2015.02.017

Cited by 18 publications

(10 citation statements)

References 36 publications

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“…The protein samples (30 μg) were loaded on 12% SDS-PAGE gel for 30 min, and migrated onto PVDF membranes for 60 min (Millipore, MA, USA). Membranes were blocked with 5% nonfat dry milk for 2 h at room temperature and incubated with polyclonal rabbit anti-CLR antibody (1:1,000 dilution; bs-1860R; RRID: AB_10855106; Bioss, Beijing, China) ( Toriyama et al., 2015 ), beta-actin antibody (1:1,500 dilution; AA128; Beyotime Institute of Biotechnology, Shanghai, China) at 4°C for 1 night. Then the PDVF membranes were rinsed in TBST solution for three times and incubated for 1 h at room temperature in secondary antibody (HRP-conjugated goat anti-rabbit, 1:2,000 dilution; A0208; Beyotime Institute of Biotechnology, Shanghai, China); (HRP-conjugated goat anti-rat, 1:2,000 dilution; A0216; Beyotime Institute of Biotechnology, Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Role of Calcitonin Gene-Related Peptide in Nociceptive Modulationin Anterior Cingulate Cortex of Naïve Rats and Rats With Inflammatory Pain

Hou

Wang

et al. 2020

Front. Pharmacol.

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It is known that calcitonin gene-related peptide (CGRP) plays a key role in pain modulation in the brain. There are high expressions of CGRP and CGRP receptor in anterior cingulate cortex (ACC), an important brain structure in pain modulation. The present study explored the role and mechanisms of CGRP and CGRP receptor in nociceptive modulation in ACC in naïve rats and inflammatory rats. Administration of different does of CGRP in ACC induced significant antinociception in a dose-dependent manner in both naïve rats and rats with inflammatory pain. The CGRP-induced antinociception was attenuated by injection of the CGRP receptor antagonist CGRP8-37 in ACC. Interestingly, both CGRP-induced antinociception and CGRP receptor expression decreased in ACC in rats with inflammatory pain compared with naïve rats. Knockdown of CGRP receptor in ACC by siRNA targeting to CGRP receptor attenuated both the CGRP receptor expression and the CGRP-induced antinociception significantly in rats. These findings demonstrate that CGRP and CGRP receptor participate in nociceptive modulation in ACC in rats, inhibiting CGRP receptor expression induces decrease in CGRP-induced antinociception in ACC.

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Section: Methodsmentioning

confidence: 99%

Role of Calcitonin Gene-Related Peptide in Nociceptive Modulationin Anterior Cingulate Cortex of Naïve Rats and Rats With Inflammatory Pain

Hou

Wang

et al. 2020

Front. Pharmacol.

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“…Specifically, the retinal arterial vasculature is derived from the internal carotid artery, and is regulated by neuropeptides like calcitonin gene-related peptide (CGRP) that are involved in migraine. [13][14][15][16] Retinal choroidal vasculature is regulated by autonomic and trigeminal sensory nerve fiber inputs that also play a role in the pathophysiology of migraine. [17][18][19] Furthermore, the optic nerve represents a direct neural connection to the brain and changes in optic nerve structure and function occur in response to changes in intracranial pressure.…”

Section: Backg Rou N Dmentioning

confidence: 99%

“…Additionally, similar vascular and autonomic nervous system pathways involved in migraine may affect the eye. Specifically, the retinal arterial vasculature is derived from the internal carotid artery, and is regulated by neuropeptides like calcitonin gene‐related peptide (CGRP) that are involved in migraine 13–16 . Retinal choroidal vasculature is regulated by autonomic and trigeminal sensory nerve fiber inputs that also play a role in the pathophysiology of migraine 17–19 .…”

Section: Introductionmentioning

confidence: 99%

Reduction in retinal microvascular perfusion during migraine attacks

Podraza,

Bangera,

Feliz

et al. 2023

Headache

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ObjectiveTo determine if there are changes in structure and function of the retinal vasculature during and between migraine attacks using optical coherence tomography angiography (OCTA).BackgroundMigraine attacks commonly include visual symptoms, but the potential role of the retina in these symptoms is not well understood. OCTA is a rapid, non‐invasive imaging technique that is used to visualize the retinal microvasculature with high spatial resolution in a clinical setting. In this study we used OCTA to quantify different features of the retinal vasculature in patients with migraine during and between attacks, as well as in healthy controls (HCs).MethodsWe performed a prospective cohort study of 37 patients with migraine with aura (MA) (median [interquartile range, IQR] age of 37 [14] years, 86% female) and 30 with migraine without aura (MO) (median [IQR] age of 37 [17] years, 77% female) and 20 HCs (median [IQR] age of 35 [7] years, 50% female). Macular OCTA scans were obtained for all participants for the interictal analysis. In 12 MA and eight MO, scans were captured both during and outside of migraine attacks and five HCs had initial and repeat scans. In addition to analyzing the morphology of the foveal avascular zone, we calculated the vessel flux index (VFI), which is an indicator of retinal perfusion and conventional metrics (such as vessel area density) in the foveal and parafoveal regions.ResultsThere was a significant difference in the parafoveal VFI in the ictal state between the groups (p = 0.009). During migraine attacks there was a significant reduction in the parafoveal region VFI in MA (−7%, 95% confidence interval [CI] −10% to −4%; p = 0.006) and MO (−7%, 95% CI −10% to −3%; p = 0.016) from their interictal baseline as compared to the change between repeat scans in HCs (2%, 95% CI −3% to 7%). Interictally, there was a mean (standard deviation [SD]) 13% (10%) (p = 0.003) lower blood perfusion in the MA group as compared to the MO group in the foveal region (mean [SD] 0.093 [0.023] vs. 0.107 [0.021], p = 0.003). Interictal analysis also revealed higher circularity in the superficial foveal avascular zone in the MA group compared with the MO group (mean [SD] 0.686 [0.088] vs. 0.629 [0.120], p = 0.004). In addition, interictal analysis of the patients with MA or MO and unilateral headache showed increased retinal vascular parameters consistent with greater perfusion in the eye ipsilateral to the side of the pain as compared with the contralateral eye.ConclusionsThese results indicate that perfusion is reduced in MA and MO in the parafoveal retina during the ictal period. Interictally, the foveal retina in MA has reduced perfusion when compared to the foveal retina in MO. Patients with unilateral headache showed interictal asymmetry of retinal perfusion between eyes. These results indicate that changes in retinal perfusion could be a part of migraine pathophysiology, and that distinct retinal vascular signatures identified with OCTA could represent biomarkers for migraine.

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“…α-MSH is produced by RPE, and its expression can be upregulated in an autocrine fashion as well as induced in macrophages [18]. Other soluble factors that maintain the immunosuppressive environment of the AqH include interleukin 10 (IL-10), PEDF [19], calcitonin gene-related peptide (CGRP) [20,21], complement regulatory proteins (CD59, membrane cofactor protein (MCP, CD46), decay accelerating factor (DAF, CD55)) [22,23], migration inhibitory factor (MIF) [24], neuropeptide Y (NPY), somatostatin (SOM) [25], and VIP [18,26]. [18].…”

Section: Soluble Immunosuppressive Moleculesmentioning

confidence: 99%

Corneal Allografts: Factors for and against Acceptance

Sakowska

Glasner

Zieliński

et al. 2021

Journal of Immunology Research

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Cornea is one of the most commonly transplanted tissues worldwide. However, it is usually omitted in the field of transplantology. Transplantation of the cornea is performed to treat many ocular diseases. It restores eyesight significantly improving the quality of life. Advancements in banking of explanted corneas and progressive surgical techniques increased availability and outcomes of transplantation. Despite the vast growth in the field of transplantation laboratory testing, standards for corneal transplantation still do not include HLA typing or alloantibody detection. This standard practice is based on immune privilege dogma that accounts for high success rates of corneal transplantation. However, the increasing need for retransplantation in high-risk patients with markedly higher risk of rejection causes ophthalmology transplantation centers to reevaluate their standard algorithms. In this review we discuss immune privilege mechanisms influencing the allograft acceptance and factors disrupting the natural immunosuppressive environment of the eye. Current developments in testing and immunosuppressive treatments (including cell therapies), when applied in corneal transplantation, may give very good results, decrease the possibility of rejection, and reduce the need for retransplantation, which is fairly frequent nowadays.

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Pathophysiological Function of Endogenous Calcitonin Gene–Related Peptide in Ocular Vascular Diseases

Cited by 18 publications

References 36 publications

Role of Calcitonin Gene-Related Peptide in Nociceptive Modulationin Anterior Cingulate Cortex of Naïve Rats and Rats With Inflammatory Pain

Role of Calcitonin Gene-Related Peptide in Nociceptive Modulationin Anterior Cingulate Cortex of Naïve Rats and Rats With Inflammatory Pain

Reduction in retinal microvascular perfusion during migraine attacks

Corneal Allografts: Factors for and against Acceptance

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