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Characterizing the normal proteome of human ciliary body.

Goel R, Murthy KR, Srikanth SM, Pinto SM, Bhattacharjee M, Kelkar DS, Madugundu AK, Dey G, Mohan SS, Krishna V, Prasad TsK, Chakravarti S, Harsha H, Pandey A - Clin Proteomics (2013)

Bottom Line: We identified a number of proteins that were previously not described in the ciliary body including importin 5 (IPO5), atlastin-2 (ATL2), B-cell receptor associated protein 29 (BCAP29), basigin (BSG), calpain-1 (CAPN1), copine 6 (CPNE6), fibulin 1 (FBLN1) and galectin 1 (LGALS1).We compared the plasma proteome with the ciliary body proteome and found that the large majority of proteins in the ciliary body were also detectable in the plasma while 896 proteins were unique to the ciliary body.We also classified proteins using pathway enrichment analysis and found most of proteins associated with ubiquitin pathway, EIF2 signaling, glycolysis and gluconeogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Johns Hopkins University School of Medicine, Baltimore 21205, MD, USA. pandey@jhmi.edu.

ABSTRACT

Background: The ciliary body is the circumferential muscular tissue located just behind the iris in the anterior chamber of the eye. It plays a pivotal role in the production of aqueous humor, maintenance of the lens zonules and accommodation by changing the shape of the crystalline lens. The ciliary body is the major target of drugs against glaucoma as its inhibition leads to a drop in intraocular pressure. A molecular study of the ciliary body could provide a better understanding about the pathophysiological processes that occur in glaucoma. Thus far, no large-scale proteomic investigation has been reported for the human ciliary body.

Results: In this study, we have carried out an in-depth LC-MS/MS-based proteomic analysis of normal human ciliary body and have identified 2,815 proteins. We identified a number of proteins that were previously not described in the ciliary body including importin 5 (IPO5), atlastin-2 (ATL2), B-cell receptor associated protein 29 (BCAP29), basigin (BSG), calpain-1 (CAPN1), copine 6 (CPNE6), fibulin 1 (FBLN1) and galectin 1 (LGALS1). We compared the plasma proteome with the ciliary body proteome and found that the large majority of proteins in the ciliary body were also detectable in the plasma while 896 proteins were unique to the ciliary body. We also classified proteins using pathway enrichment analysis and found most of proteins associated with ubiquitin pathway, EIF2 signaling, glycolysis and gluconeogenesis.

Conclusions: More than 95% of the identified proteins have not been previously described in the ciliary body proteome. This is the largest catalogue of proteins reported thus far in the ciliary body that should provide new insights into our understanding of the factors involved in maintaining the secretion of aqueous humor. The identification of these proteins will aid in understanding various eye diseases of the anterior segment such as glaucoma and presbyopia.

No MeSH data available.


Related in: MedlinePlus

Comparison of the ciliary body proteome with the aqueous humor and plasma proteome. Panel A shows comparison of the ciliary body proteins with plasma proteins annotated in the Plasma Proteome Database. Panel B depicts comparison of the ciliary body proteome with aqueous humor proteome annotated from the published literature. Panel C shows a comparison of proteins that are common to the ciliary body and plasma with those that are common to the ciliary body and the aqueous humor.
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Figure 4: Comparison of the ciliary body proteome with the aqueous humor and plasma proteome. Panel A shows comparison of the ciliary body proteins with plasma proteins annotated in the Plasma Proteome Database. Panel B depicts comparison of the ciliary body proteome with aqueous humor proteome annotated from the published literature. Panel C shows a comparison of proteins that are common to the ciliary body and plasma with those that are common to the ciliary body and the aqueous humor.

Mentions: The fenestrated ciliary body capillary endothelia allow the flow of blood plasma across the ciliary stroma which helps in the secretion of aqueous humor by the ciliary epithelium. We were interested in proteins derived from ciliary body, which are directly relevant to its physiology, and not those derived from the blood diffusing into the ciliary body. There is a blood aqueous barrier, which permits solutes from the blood vessels of the ciliary stroma into the aqueous humor [11]. We compared the ciliary body proteome with human plasma proteome from Plasma Proteome Database [43] and aqueous humor proteome in order to get the ciliary body specific proteins. A total of 9,393 plasma proteins were compared with the ciliary body proteome and we observed that 896 proteins were unique to the ciliary body proteome as seen in Figure 4A. Proteins detected in the ciliary body were also compared to proteins previously reported in the aqueous humor [7,44-47]. We found 211 proteins that were also reported in the aqueous humor proteome Figure 4B. Only seven of these 211 proteins were described in the plasma (Figure 4C). These unique proteins are CRYGD crystallin, gamma D (CRYGD), crystallin, gamma S (CRYGS) and crystallin, gamma C (CRYGC), which maintain the transparency and refractive index of the lens [48,49]. Gamma crystallins have been involved in cataract formation due to aging or mutations. The source of these proteins is likely to be the aqueous humor and not the plasma, as the lens, where these are abundant is an avascular structure receiving all its nutrient supply from the aqueous humor. In addition the aqueous humor removes metabolic waste from the lens. Another molecule is pyruvate kinase muscle (PKM), which is involved in glycolysis and serves as a key regulator of energy metabolism in proliferating cells. Frizzled-related protein (FRZB) is secreted protein and plays a significant role in the loss of the Wnt signaling pathway in different type of cancers by down regulation of this gene [50]. Ubiquitin fusion degradation 1 (UFD1L) forms complex with nuclear protein localization 4 (NPLOC4) and valosin containing protein (VCP). NPLOC4 and VCP are also identified in this study. This complex is required for the degradation of ubiquitinated proteins [51]. Retinoschisin 1 (RS1) plays a significant role in the cellular organization of the retina [44,45].


Characterizing the normal proteome of human ciliary body.

Goel R, Murthy KR, Srikanth SM, Pinto SM, Bhattacharjee M, Kelkar DS, Madugundu AK, Dey G, Mohan SS, Krishna V, Prasad TsK, Chakravarti S, Harsha H, Pandey A - Clin Proteomics (2013)

Comparison of the ciliary body proteome with the aqueous humor and plasma proteome. Panel A shows comparison of the ciliary body proteins with plasma proteins annotated in the Plasma Proteome Database. Panel B depicts comparison of the ciliary body proteome with aqueous humor proteome annotated from the published literature. Panel C shows a comparison of proteins that are common to the ciliary body and plasma with those that are common to the ciliary body and the aqueous humor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750387&req=5

Figure 4: Comparison of the ciliary body proteome with the aqueous humor and plasma proteome. Panel A shows comparison of the ciliary body proteins with plasma proteins annotated in the Plasma Proteome Database. Panel B depicts comparison of the ciliary body proteome with aqueous humor proteome annotated from the published literature. Panel C shows a comparison of proteins that are common to the ciliary body and plasma with those that are common to the ciliary body and the aqueous humor.
Mentions: The fenestrated ciliary body capillary endothelia allow the flow of blood plasma across the ciliary stroma which helps in the secretion of aqueous humor by the ciliary epithelium. We were interested in proteins derived from ciliary body, which are directly relevant to its physiology, and not those derived from the blood diffusing into the ciliary body. There is a blood aqueous barrier, which permits solutes from the blood vessels of the ciliary stroma into the aqueous humor [11]. We compared the ciliary body proteome with human plasma proteome from Plasma Proteome Database [43] and aqueous humor proteome in order to get the ciliary body specific proteins. A total of 9,393 plasma proteins were compared with the ciliary body proteome and we observed that 896 proteins were unique to the ciliary body proteome as seen in Figure 4A. Proteins detected in the ciliary body were also compared to proteins previously reported in the aqueous humor [7,44-47]. We found 211 proteins that were also reported in the aqueous humor proteome Figure 4B. Only seven of these 211 proteins were described in the plasma (Figure 4C). These unique proteins are CRYGD crystallin, gamma D (CRYGD), crystallin, gamma S (CRYGS) and crystallin, gamma C (CRYGC), which maintain the transparency and refractive index of the lens [48,49]. Gamma crystallins have been involved in cataract formation due to aging or mutations. The source of these proteins is likely to be the aqueous humor and not the plasma, as the lens, where these are abundant is an avascular structure receiving all its nutrient supply from the aqueous humor. In addition the aqueous humor removes metabolic waste from the lens. Another molecule is pyruvate kinase muscle (PKM), which is involved in glycolysis and serves as a key regulator of energy metabolism in proliferating cells. Frizzled-related protein (FRZB) is secreted protein and plays a significant role in the loss of the Wnt signaling pathway in different type of cancers by down regulation of this gene [50]. Ubiquitin fusion degradation 1 (UFD1L) forms complex with nuclear protein localization 4 (NPLOC4) and valosin containing protein (VCP). NPLOC4 and VCP are also identified in this study. This complex is required for the degradation of ubiquitinated proteins [51]. Retinoschisin 1 (RS1) plays a significant role in the cellular organization of the retina [44,45].

Bottom Line: We identified a number of proteins that were previously not described in the ciliary body including importin 5 (IPO5), atlastin-2 (ATL2), B-cell receptor associated protein 29 (BCAP29), basigin (BSG), calpain-1 (CAPN1), copine 6 (CPNE6), fibulin 1 (FBLN1) and galectin 1 (LGALS1).We compared the plasma proteome with the ciliary body proteome and found that the large majority of proteins in the ciliary body were also detectable in the plasma while 896 proteins were unique to the ciliary body.We also classified proteins using pathway enrichment analysis and found most of proteins associated with ubiquitin pathway, EIF2 signaling, glycolysis and gluconeogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Johns Hopkins University School of Medicine, Baltimore 21205, MD, USA. pandey@jhmi.edu.

ABSTRACT

Background: The ciliary body is the circumferential muscular tissue located just behind the iris in the anterior chamber of the eye. It plays a pivotal role in the production of aqueous humor, maintenance of the lens zonules and accommodation by changing the shape of the crystalline lens. The ciliary body is the major target of drugs against glaucoma as its inhibition leads to a drop in intraocular pressure. A molecular study of the ciliary body could provide a better understanding about the pathophysiological processes that occur in glaucoma. Thus far, no large-scale proteomic investigation has been reported for the human ciliary body.

Results: In this study, we have carried out an in-depth LC-MS/MS-based proteomic analysis of normal human ciliary body and have identified 2,815 proteins. We identified a number of proteins that were previously not described in the ciliary body including importin 5 (IPO5), atlastin-2 (ATL2), B-cell receptor associated protein 29 (BCAP29), basigin (BSG), calpain-1 (CAPN1), copine 6 (CPNE6), fibulin 1 (FBLN1) and galectin 1 (LGALS1). We compared the plasma proteome with the ciliary body proteome and found that the large majority of proteins in the ciliary body were also detectable in the plasma while 896 proteins were unique to the ciliary body. We also classified proteins using pathway enrichment analysis and found most of proteins associated with ubiquitin pathway, EIF2 signaling, glycolysis and gluconeogenesis.

Conclusions: More than 95% of the identified proteins have not been previously described in the ciliary body proteome. This is the largest catalogue of proteins reported thus far in the ciliary body that should provide new insights into our understanding of the factors involved in maintaining the secretion of aqueous humor. The identification of these proteins will aid in understanding various eye diseases of the anterior segment such as glaucoma and presbyopia.

No MeSH data available.


Related in: MedlinePlus