Limits...
Intravitreal injection of β -crystallin B2 improves retinal ganglion cell survival in an experimental animal model of glaucoma

View Article: PubMed Central - PubMed

ABSTRACT

Purpose of this study was to investigate firstly specific proteomic changes within the retina in the course of an animal glaucoma model and to identify secondly new approaches for neuroprotective, therapeutic options in glaucoma by addressing those specific changes. Intraocular pressure was elevated through cauterization of episcleral veins in adult Sprague Dawley rats. Molecular and morphological changes were surveyed using mass spectrometry, optical coherence tomography as well as immunohistochemical cross section- and flat mount stainings. By quantifying more than 1500 retinal proteins, it was found that the HspB5 protein and numerous beta-crystallins showed a uniform and unique shifting expression pattern as a result of different periods of elevated IOP exposure. Crystallins showed a significant downregulation (p<0.05) after 3 weeks of elevated IOP and an upregulation after 7 weeks. Counteracting those typical changes, an intravitreal injection of β-crystallin B2 at the time of IOP elevation was found to reduce retinal ganglion cell loss (p<0.05), decrease of the retinal nerve fiber layer (p<0.05) and impairment of the optic nerve. Ultimately, proteomic data revealed that β-crystallin B2 might influence calcium-depended cell signaling pathways with severe effect on apoptosis and gene regulation. In this context especially annexin A5, calcium-transporting ATPase 1 and various histone proteins seem to play a major role.

No MeSH data available.


Related in: MedlinePlus

Regulatory changes of crystallin proteins on elevated IOP.Analyzed members of the different crystallin subclasses showed a unique expression profile at both investigated timepoints of IOP elevation (t1 n = 8, t2 n = 7). (*p<0.05, **p<0.01, Mann-Whitney U test, ±SEM). Fold-changes are plotted using a logarithmic scale with a basis of 2.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5383327&req=5

pone.0175451.g003: Regulatory changes of crystallin proteins on elevated IOP.Analyzed members of the different crystallin subclasses showed a unique expression profile at both investigated timepoints of IOP elevation (t1 n = 8, t2 n = 7). (*p<0.05, **p<0.01, Mann-Whitney U test, ±SEM). Fold-changes are plotted using a logarithmic scale with a basis of 2.

Mentions: The mass-spectrometric profiling revealed regulatory changes in the expression of crystallin proteins. Interestingly, all α- and β-crystallin proteins were found to be down-regulated after three weeks of elevated IOP and up-regulated after seven weeks of IOP elevation (Fig 3).


Intravitreal injection of β -crystallin B2 improves retinal ganglion cell survival in an experimental animal model of glaucoma
Regulatory changes of crystallin proteins on elevated IOP.Analyzed members of the different crystallin subclasses showed a unique expression profile at both investigated timepoints of IOP elevation (t1 n = 8, t2 n = 7). (*p<0.05, **p<0.01, Mann-Whitney U test, ±SEM). Fold-changes are plotted using a logarithmic scale with a basis of 2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383327&req=5

pone.0175451.g003: Regulatory changes of crystallin proteins on elevated IOP.Analyzed members of the different crystallin subclasses showed a unique expression profile at both investigated timepoints of IOP elevation (t1 n = 8, t2 n = 7). (*p<0.05, **p<0.01, Mann-Whitney U test, ±SEM). Fold-changes are plotted using a logarithmic scale with a basis of 2.
Mentions: The mass-spectrometric profiling revealed regulatory changes in the expression of crystallin proteins. Interestingly, all α- and β-crystallin proteins were found to be down-regulated after three weeks of elevated IOP and up-regulated after seven weeks of IOP elevation (Fig 3).

View Article: PubMed Central - PubMed

ABSTRACT

Purpose of this study was to investigate firstly specific proteomic changes within the retina in the course of an animal glaucoma model and to identify secondly new approaches for neuroprotective, therapeutic options in glaucoma by addressing those specific changes. Intraocular pressure was elevated through cauterization of episcleral veins in adult Sprague Dawley rats. Molecular and morphological changes were surveyed using mass spectrometry, optical coherence tomography as well as immunohistochemical cross section- and flat mount stainings. By quantifying more than 1500 retinal proteins, it was found that the HspB5 protein and numerous beta-crystallins showed a uniform and unique shifting expression pattern as a result of different periods of elevated IOP exposure. Crystallins showed a significant downregulation (p&lt;0.05) after 3 weeks of elevated IOP and an upregulation after 7 weeks. Counteracting those typical changes, an intravitreal injection of &beta;-crystallin B2 at the time of IOP elevation was found to reduce retinal ganglion cell loss (p&lt;0.05), decrease of the retinal nerve fiber layer (p&lt;0.05) and impairment of the optic nerve. Ultimately, proteomic data revealed that &beta;-crystallin B2 might influence calcium-depended cell signaling pathways with severe effect on apoptosis and gene regulation. In this context especially annexin A5, calcium-transporting ATPase 1 and various histone proteins seem to play a major role.

No MeSH data available.


Related in: MedlinePlus