Human lacrimal gland regeneration: Perspectives and review of literature

Tiwari, Shubha; Ali, Mohammad Javed; Vemuganti, Geeta K.

doi:10.1016/j.sjopt.2013.09.004

Cited by 39 publications

(31 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have evaluated adult human lacrimal glands (Paulsen, 2006;Tiwari et al, 2012Tiwari et al, , 2014. Although the morphological development of the early human lacrimal gland has been described (de la Cuadra-Blanco et al, 2003), to our knowledge no study has investigated the molecular characteristics of the human fetal lacrimal gland or whether its cell identities are similar to the mouse.…”

Section: Molecular Profiling Of Human Fetal Lacrimal Glandsmentioning

confidence: 99%

Defining epithelial cell dynamics and lineage relationships in the developing lacrimal gland

et al. 2017

View full text Add to dashboard Cite

The tear-producing lacrimal gland is a tubular organ that protects and lubricates the ocular surface. The lacrimal gland possesses many features that make it an excellent model in which to investigate tubulogenesis, but the cell types and lineage relationships that drive lacrimal gland formation are unclear. Using single-cell sequencing and other molecular tools, we reveal novel cell identities and epithelial lineage dynamics that underlie lacrimal gland development. We show that the lacrimal gland from its earliest developmental stages is composed of multiple subpopulations of immune, epithelial and mesenchymal cell lineages. The epithelial lineage exhibits the most substantial cellular changes, transitioning through a series of unique transcriptional states to become terminally differentiated acinar, ductal and myoepithelial cells. Furthermore, lineage tracing in postnatal and adult glands provides the first direct evidence of unipotent KRT5 + epithelial cells in the lacrimal gland. Finally, we show conservation of developmental markers between the developing mouse and human lacrimal gland, supporting the use of mice to understand human development. Together, our data reveal crucial features of lacrimal gland development that have broad implications for understanding epithelial organogenesis.

show abstract

Section: Molecular Profiling Of Human Fetal Lacrimal Glandsmentioning

confidence: 99%

Defining epithelial cell dynamics and lineage relationships in the developing lacrimal gland

et al. 2017

View full text Add to dashboard Cite

show abstract

“…[16][17][18][19] In healthy lacrimal glands, ECM maturates, persuading the differentiation of the epithelial cells and restoration of lacrimal gland acinar structure integrity. 20 During pathological conditions, ECM triggers signaling mechanisms for selective development and differentiation during tissue injury and repair processes. 21 Increased degradation of ECM structures of the lacrimal gland has been implicated in the pathogenesis of Sjögren's syndrome.…”

mentioning

confidence: 99%

Role of Matrix Metalloproteinases 2 and 9 in Lacrimal Gland Disease in Animal Models of Sjögren's Syndrome

Aluri

Kublin

Thotakura

et al. 2015

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Citation: Aluri HS, Kublin CL, Thotakura S, et al. Role of matrix metalloproteinases 2 and 9 in lacrimal gland disease in animal models of Sjögren's syndrome. Invest Ophthalmol Vis Sci. 2015;56:5218-5228. DOI:10.1167/ iovs.15-17003 PURPOSE. Chronic inflammation of the lacrimal gland results in changes in the composition of the extracellular matrix (ECM), which is believed to compromise tissue repair. We hypothesized that increased production/activity of matrix metalloproteinases (MMPs), especially MMP-2 and -9, in inflamed lacrimal glands modifies the ECM environment, therefore disrupting tissue repair.METHODS. The lacrimal glands from female MRL/lpr and male NOD mice along with their respective control strains were harvested and divided into three pieces and processed for histology, immunohistochemistry, zymography, Western blotting, and RNA analyses. In another study, MRL/lpr mice were treated for 5 weeks with a selective MMP2/9 inhibitor peptide or a control peptide. At the end of treatment, the lacrimal glands were excised and the tissue was processed as described above.RESULTS. There was a 2.5-and 2.7-fold increase in MMP2 gene expression levels in MRL/lpr and NOD mice, respectively. Matrix metalloproteinase 2 and 9 enzymatic activities and protein expression levels were significantly upregulated in the lacrimal glands of MRL/lpr and NOD mice compared to controls. Treatment with the MMP2/9 inhibitor resulted in decreased activity of MMP-2 and -9 both in vitro and in vivo. Importantly, MMP2/9 inhibitor treatment of MRL/lpr mice improved aqueous tear production and resulted in reduced number and size of lymphocytic foci in diseased lacrimal glands.CONCLUSIONS. We conclude that MMP2/9 expression and activity are elevated in lacrimal glands of two murine models of Sjögren's syndrome, suggesting that manipulation of MMP2/9 activity might be a potential therapeutic target in chronically inflamed lacrimal glands.

show abstract

“…41 In diseased glands, the ECM is remodeling constantly, and epithelial differentiation stays incomplete and LG acinar structure remains unrestored. 9,10,12 Thus, the diseased/chronically inflamed state of the LG and other exocrine glands could be due to abnormal ECM maturation, 32,[42][43][44] which may affect activation or differentiation of LG stem/progenitor cells.…”

mentioning

confidence: 99%

Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

Umazume

Thomas

Campbell

et al. 2015

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. The adult lacrimal gland (LG) is highly regenerative and is able to repair itself even after substantial damage; however, this ability to regenerate is lost with the development of dry eye conditions in chronically inflamed LGs.This study compares changes in the cell adhesion and cell matrix molecules and stem cell transcription factors in the LGs of healthy mice and of two mouse models of Sjögren's syndrome: nonobese diabetic (NOD) and MRLlpr/lpr (MRL/lpr) mice during the early stage of inflammation. METHODS. TheLGs from 12-to 13-week-old female MRL/lpr and male NOD mice along with their respective control strains were harvested and divided into three pieces and processed for quantitative (q) RT-PCR and qRT-PCR Arrays, histology, immunohistochemistry, and Western blotting. RESULTS. The extracellular matrix (ECM) and adhesion molecules RT2 -PCR array combined with protein expression data revealed changes in the expression of integrins, matrix metalloproteinases, and other molecules, which are associated largely with invasion, attachment, and expansion of the lymphocytic cells, whereas changes in the stem cell transcription factors revealed substantial decrease in expression of transcription factors associated with epithelial stem/progenitor cell lineage. CONCLUSIONS.We concluded that the expression of several important ECM components is significantly deregulated in the LG of two murine models of Sjögren's syndrome, suggesting an alteration of the epithelial stem/progenitor cell niche. This may result in profound effects on localization, activation, proliferation, and differentiation of the LG stem/progenitor cells and, therefore, LG regeneration.

show abstract

Human lacrimal gland regeneration: Perspectives and review of literature

Cited by 39 publications

References 25 publications

Defining epithelial cell dynamics and lineage relationships in the developing lacrimal gland

Defining epithelial cell dynamics and lineage relationships in the developing lacrimal gland

Role of Matrix Metalloproteinases 2 and 9 in Lacrimal Gland Disease in Animal Models of Sjögren's Syndrome

Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

Contact Info

Product

Resources

About