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Structure and function of mouse lens suture examined by 2-photon fluorescence microscopic imaging.

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Title: Structure and function of mouse lens suture examined by 2-photon fluorescence microscopic imaging.
Authors: Zhang Q; Department of Physics, University of California, Berkeley, CA, 94720, USA.; Department of Biomedical Engineering, College of Biomedicine, City University of Hong Kong, Kowloon, Hong Kong SAR, China., Zhu J; Department of Neuroscience, University of California, Berkeley, CA, 94720, USA., Painter T; Herbert Wertheim School of Optometry, University of California, Berkeley, CA, 94720, USA.; Vision Science Program, University of California, Berkeley, CA, 94720, USA., Xia CH; Herbert Wertheim School of Optometry, University of California, Berkeley, CA, 94720, USA.; Vision Science Program, University of California, Berkeley, CA, 94720, USA., Ji N; Department of Physics, University of California, Berkeley, CA, 94720, USA.; Department of Neuroscience, University of California, Berkeley, CA, 94720, USA.; Helen Wills Neuroscience Institute, University of California, Berkeley, CA, 94720, USA.; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA., Gong X; Herbert Wertheim School of Optometry, University of California, Berkeley, CA, 94720, USA. xgong@berkeley.edu.; Vision Science Program, University of California, Berkeley, CA, 94720, USA. xgong@berkeley.edu.
Source: Scientific reports [Sci Rep] 2026 Mar 24; Vol. 16 (1). Date of Electronic Publication: 2026 Mar 24.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
Imprint Name(s): Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms: Lens, Crystalline*/diagnostic imaging , Lens, Crystalline*/metabolism , Lens, Crystalline*/pathology , Lens, Crystalline*/ultrastructure , Cataract*/pathology , Cataract*/diagnostic imaging , Microscopy, Fluorescence, Multiphoton*/methods, Animals ; Mice ; Mice, Knockout ; Microscopy, Fluorescence
Abstract: We used two-photon fluorescence microscopy (2PFM) to examine lens fiber and suture architecture, as well as permeability, in wild-type (WT) lenses and in lenses from klotho-like protein homology (KLPH) knockout (KLPH-KO) mice. KLPH is a type I membrane glycoprotein encoded by the Lctl gene; KLPH-KO mice develop lens suture cataracts. Lens sutures have been hypothesized to serve as pathways for transporting ions, nutrients, and other factors as part of the lens microcirculation required to maintain homeostasis and transparency. Three-dimensional (3D) in vivo imaging revealed typical "Y" and "double-Y" anterior suture geometries, along with depth-dependent variation, in WT lenses. In contrast, KLPH-KO lenses exhibited markedly heterogeneous suture morphologies and misalignment between the anterior and posterior suture planes. Quantification of pattern variability using the mean structural similarity index (SSIM) of individual z-stacks relative to the stack mean projection revealed a significant increase in pattern randomization in KLPH-KO lenses (p < 0.05). Both WT and KLPH-KO lenses displayed voids near sutures and enlarged vacuoles distributed throughout the lens in vivo. Notably, KLPH-KO lenses exhibited irregular, enlarged central voids containing ~ 2-5 μm amorphous structures, consistent with subcellular remnants and/or membrane-associated aggregates. In conclusion, this study provides novel morphological markers for characterizing suture cataracts and associated fiber pathology. It further demonstrates that the dye-impermeable lens suture represents a stabilized interface formed by elongated fiber ends, supporting lens integrity and maintaining the organization of lens fibers.
(© 2026. The Author(s).)
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
Comments: Update of: bioRxiv. 2025 Nov 07:2025.09.08.675023. doi: 10.1101/2025.09.08.675023.. (PMID: 41030987)
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Grant Information: T32 EY007043 United States EY NEI NIH HHS; U01 NS118300 United States NS NINDS NIH HHS
Entry Date(s): Date Created: 20260325 Date Completed: 20260713 Latest Revision: 20260726
Update Code: 20260726
PubMed Central ID: PMC13168428
DOI: 10.1038/s41598-026-45299-2
PMID: 41876809
Database: MEDLINE
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  Data: We used two-photon fluorescence microscopy (2PFM) to examine lens fiber and suture architecture, as well as permeability, in wild-type (WT) lenses and in lenses from klotho-like protein homology (KLPH) knockout (KLPH-KO) mice. KLPH is a type I membrane glycoprotein encoded by the Lctl gene; KLPH-KO mice develop lens suture cataracts. Lens sutures have been hypothesized to serve as pathways for transporting ions, nutrients, and other factors as part of the lens microcirculation required to maintain homeostasis and transparency. Three-dimensional (3D) in vivo imaging revealed typical &quot;Y&quot; and &quot;double-Y&quot; anterior suture geometries, along with depth-dependent variation, in WT lenses. In contrast, KLPH-KO lenses exhibited markedly heterogeneous suture morphologies and misalignment between the anterior and posterior suture planes. Quantification of pattern variability using the mean structural similarity index (SSIM) of individual z-stacks relative to the stack mean projection revealed a significant increase in pattern randomization in KLPH-KO lenses (p &amp;lt; 0.05). Both WT and KLPH-KO lenses displayed voids near sutures and enlarged vacuoles distributed throughout the lens in vivo. Notably, KLPH-KO lenses exhibited irregular, enlarged central voids containing ~ 2-5&#160;μm amorphous structures, consistent with subcellular remnants and/or membrane-associated aggregates. In conclusion, this study provides novel morphological markers for characterizing suture cataracts and associated fiber pathology. It further demonstrates that the dye-impermeable lens suture represents a stabilized interface formed by elongated fiber ends, supporting lens integrity and maintaining the organization of lens fibers.&lt;br /&gt; (&#169; 2026. The Author(s).)
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  Data: Declarations. Competing interests: The authors declare no competing interests.
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  Data: Kuszak, J. &amp; Costello, M. J. Cambridge,. The structure of the vertebrate lens. in Development of the Ocular Lens 71–118 (2004).&lt;br /&gt;Bassnett, S., Shi, Y. &amp; Vrensen, G. F. Biological glass: structural determinants of eye lens transparency. Philos. Trans. R. Soc. Lond. B Biol. Sci. 366, 1250–1264 (2011). (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2210%2E1098%2Frstb%2E2010%2E0302214025843061108%22&quot;&gt;10.1098/rstb.2010.0302214025843061108)&lt;/searchLink&gt;&lt;br /&gt;Bassnett, S. &amp; Sikic, H. The lens growth process. Prog. Retin. Eye Res. 60, 181–200 (2017). (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2210%2E1016%2Fj%2Epreteyeres%2E2017%2E04%2E001284111235605917%22&quot;&gt;10.1016/j.preteyeres.2017.04.001284111235605917)&lt;/searchLink&gt;&lt;br /&gt;Greiling, T. M., Clark, J. M. &amp; Clark, J. I. The significance of growth shells in development of symmetry, transparency, and refraction of the human lens. Front. Ophthalmol. (Lausanne). 4, 1434327 (2024). (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2210%2E3389%2Ffopht%2E2024%2E14343273910014011294239%22&quot;&gt;10.3389/fopht.2024.14343273910014011294239)&lt;/searchLink&gt;&lt;br /&gt;Cheng, C., Ansari, M. M., Cooper, J. A. &amp; Gong, X. EphA2 and Src regulate equatorial cell morphogenesis during lens development. Development 140, 4237–4245 (2013). (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2210%2E1242%2Fdev%2E100727240261203787762%22&quot;&gt;10.1242/dev.100727240261203787762)&lt;/searchLink&gt;&lt;br /&gt;Sugiyama, Y., Lovicu, F. J. &amp; McAvoy, J. W. Planar cell polarity in the mammalian eye lens. Organogenesis 7, 191–201 (2011). (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2210%2E4161%2Forg%2E7%2E3%2E18421220275403243032%22&quot;&gt;10.4161/org.7.3.18421220275403243032)&lt;/searchLink&gt;&lt;br /&gt;Hayes, J. M. et al. 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  Data: 10.1038/s41598-026-45299-2
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        Value: 10.1038/s41598-026-45299-2
    Languages:
      – Code: eng
        Text: English
    Subjects:
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Mice, Knockout
        Type: general
      – SubjectFull: Microscopy, Fluorescence
        Type: general
      – SubjectFull: Lens, Crystalline diagnostic imaging
        Type: general
      – SubjectFull: Lens, Crystalline metabolism
        Type: general
      – SubjectFull: Lens, Crystalline pathology
        Type: general
      – SubjectFull: Lens, Crystalline ultrastructure
        Type: general
      – SubjectFull: Cataract pathology
        Type: general
      – SubjectFull: Cataract diagnostic imaging
        Type: general
      – SubjectFull: Microscopy, Fluorescence, Multiphoton methods
        Type: general
    Titles:
      – TitleFull: Structure and function of mouse lens suture examined by 2-photon fluorescence microscopic imaging.
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            – D: 24
              M: 03
              Text: 2026 Mar 24
              Type: published
              Y: 2026
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            – Type: issn-electronic
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            – TitleFull: Scientific reports
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