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Graefe's Archive for Clinical and Experimental Ophthalmology

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Open Access 01-02-2019 | Basic Science

Developmental and age-related changes to the elastic lamina of Bruch’s membrane in mice

Authors: Hidetsugu Mori, Haruhiko Yamada, Keiko Toyama, Kanji Takahashi, Tomoya Akama, Tadashi Inoue, Tomoyuki Nakamura

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 2/2019

Abstract

Background

Fibrillin-1, tropoelastin, fibulin-5, and latent transforming growth factor beta-binding protein-2 and protein-4 (LTBP-2 and LTBP-4) are essential proteins for the elastic lamina (EL). In this study, we analyzed each of these molecules in the EL of Bruch’s membrane (BM) through development and aging.

Methods

C57BL/6 mice (embryonic (E) days E12.5, E15.5, and E18.5; postnatal (P) days P1, P4, and P7 and P3, P6, and P75 weeks of age) were used. To investigate localization, immunohistochemical staining (IH) was performed. Transmission electron microscopy (TEM) was used to evaluate the formation of microfibrils and tropoelastin. mRNA expression was determined by quantitative real-time PCR (qRT-PCR).

Results

All five proteins were expressed in the EL of BM by IH except in embryonic mice. TEM results showed that tropoelastin co-stained with microfibrils. Between 3 and 6 weeks of age, microfibrils became longer and thicker. It was difficult to evaluate the EL of BM in senile mice at 75 weeks of age because of abundant deposits which correspond to drusen. mRNA levels of each protein increased dramatically from E15.5 to P1 days and plateaued by P3 weeks as shown by qRT-PCR.

Conclusions

In conclusion, these five proteins are possibly involved in elastic fiber assembly in BM. We define the date of full assembly of the EL of BM as 3 weeks of age in mice.

Das A, Frank RN, Zhang NL, Turczyn TJ (1990) Ultrastructural localization of extracellular matrix components in human retinal vessels and Bruch's membrane. Arch Ophthalmol 108:421–429CrossRefPubMed

Hirabayashi Y, Fujimori O, Shimizu S (2003) Bruch's membrane of the brachymorphic mouse. Med Electron Microsc 36:139–146. https://doi.org/10.1007/s00795-003-0218-z CrossRefPubMed

Booij JC, Baas DC, Beisekeeva J, Gorgels TG, Bergen AA (2010) The dynamic nature of Bruch’s membrane. Prog Retin Eye Res 29:1–18. https://doi.org/10.1016/j.preteyeres.2009.08.003 CrossRefPubMed

Guymer R, Luthert P, Bird A (1990) Changes in Bruch's membrane and related structures with age. Prog Retin Eye Res 18:59–90CrossRef

Kresse H, Schönherr E (2001) Proteoglycans of the extracellular matrix and growth control. J Cell Physiol 189:266–274. https://doi.org/10.1002/jcp.10030 CrossRefPubMed

Chong NH, Keonin J, Luthert PJ, Frennesson CI, Weingeist DM, Wolf RL et al (2005) Decreased thickness and integrity of the macular elastic layer of Bruch's membrane correspond to the distribution of lesions associated with age-related macular degeneration. Am J Pathol 166:241–251. https://doi.org/10.1016/S0002-9440(10)62248-1 CrossRefPubMedPubMedCentral

Goldberg MF (1976) Bruch’s membrane and vascular growth. Investig Ophthalmol 15:443–446

Tobe T, Ortega S, Luna JD, Ozaki H, Okamoto N, Derevjanik NL et al (1998) Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model. Am J Pathol 153:1641–1646. https://doi.org/10.1016/S0002-9440(10)65753-7 CrossRefPubMedPubMedCentral

Ryan SJ (1979) The development of an experimental model of subretinal neovascularization in disciform macular degeneration. Trans Am Ophthalmol Soc 77:707–745PubMedPubMedCentral

10.

Sakamoto T, Sanui H, Ishibashi T, Kohno T, Takahira K, Inomata H et al (1994) Subretinal neovascularization in the rat induced by IRBP synthetic peptides. Exp Eye Res 58:155–160CrossRefPubMed

11.

Spilsbury K, Garrett KL, Shen WY, Constable IJ, Rakoczy PE (2000) Overexpression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelium leads to the development of choroidal neovascularization. Am J Pathol 2000 157:135–144. Erratum in: Am J Pathol;157:1413. https://doi.org/10.1016/S0002-9440(10)64525-7 CrossRef

12.

Elizabeth Rakoczy P, Yu MJ, Nusinowitz S, Chang B, Heckenlively JR (2006) Mouse models of age-related macular degeneration. Exp Eye Res 82:741–752. https://doi.org/10.1016/j.exer.2005.10.012 CrossRefPubMed

13.

Ambati J, Anand A, Fernandez S, Sakurai E, Lynn BC, Kuziel WA et al (2003) An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat Med 9:1390–1397. https://doi.org/10.1038/nm950 CrossRefPubMed

14.

Dithmar S, Curcio CA, Le NA, Brown S, Grossniklaus HE (2000) Ultrastructural changes in Bruch's membrane of apolipoprotein E-deficient mice. Invest Ophthalmol Vis Sci 41:2035–2042PubMed

15.

Jones A, Kumar S, Zhang N, Tong Z, Yang JH, Watt C et al (2011) Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice. Proc Natl Acad Sci U S A 108:14578–14583. https://doi.org/10.1073/pnas.1102853108 CrossRefPubMedPubMedCentral

16.

Sivaprasad S, Chong NV, Bailey TA (2005) Serum elastin-derived peptides in age-related macular degeneration. Invest Ophthalmol Vis Sci 46:3046–3051. https://doi.org/10.1167/iovs.04-1277 CrossRefPubMed

17.

Nie GY, Hampton A, Li Y, Findlay JK, Salamonsen LA (2003) Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2. Biochem J 371:39–48. https://doi.org/10.1042/BJ20021569 CrossRefPubMedPubMedCentral

18.

Zurawa-Janicka D, Skorko-Glonek J, Lipinska B (2010) HtrA proteins as targets in therapy of cancer and other diseases. Expert Opin Ther Targets 14:665–679. https://doi.org/10.1517/14728222.2010.487867 CrossRefPubMed

19.

Vrhovski B, Weiss AS (1998) Biochemistry of tropoelastin. Eur J Biochem 258:1–18CrossRefPubMed

20.

Rosenbloom J, Abrams WR, Mecham R (1993) Extracellular matrix 4: the elastic fiber. FASEB J 7:1208–1218CrossRefPubMed

21.

Kielty CM, Sherratt MJ, Shuttleworth CA (2002) Elastic fibres. J Cell Sci 115:2817–2828PubMed

22.

Ramirez F, Sakai LY, Dietz HC, Rifkin DB (2004) Fibrillin microfibrils, multipurpose extracellular networks in organismal physiology. Physiol Genomics 19:151–154CrossRefPubMed

23.

Low FN (1962) Microfibrils: fine filamentous components of the tissue space. Anat Rec 142:131–137CrossRefPubMed

24.

Sakai LY, Keene DR, Glanville RW, Bächinger HP (1991) Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. J Biol Chem 266:14763–14770PubMed

25.

Sakai LY, Keene DR, Engvall E (1986) Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol 103:2499–24509CrossRefPubMed

26.

Jensen SA, Reinhardt DP, Gibson MA, Weiss AS (2001) Protein interaction studies of MAGP-1 with tropoelastin and fibrillin-1. J Biol Chem 276:39661–39666. https://doi.org/10.1074/jbc.M104533200 CrossRefPubMed

27.

Zhang H, Apfelroth SD, Hu W, Davis EC, Sanguineti C, Bonadio J et al (1994) Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices. J Cell Biol 124:855–863CrossRefPubMed

28.

Pereira L, D’Alessio M, Ramirez F, Lynch JR, Sykes B, Pangilinan T et al (1993) Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. Hum Mol Genet 2:1762CrossRefPubMed

29.

Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (2001) Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res 8:85–95CrossRefPubMed

30.

Mariencheck MC, Davis EC, Zhang H, Ramirez F, Rosenbloom J, Gibson MA et al (1995) Fibrillin-1 and fibrillin-2 show temporal and tissue-specific regulation of expression in developing elastic tissues. Connect Tissue Res 31:87–97CrossRefPubMed

31.

Carta L, Pereira L, Arteaga-Solis E, Lee-Arteaga SY, Lenart B, Starcher B et al (2006) Fibrillins 1 and 2 perform partially overlapping functions during aortic development. J Biol Chem 281:8016–8023. https://doi.org/10.1074/jbc.M511599200 CrossRefPubMed

32.

Resch MD, Schlötzer-Schrehardt U, Hofmann-Rummelt C, Kruse FE, Seitz B (2009) Alterations of epithelial adhesion molecules and basement membrane components in lattice corneal dystrophy (LCD). Graefes Arch Clin Exp Ophthalmol 247:1081–1088. https://doi.org/10.1007/s00417-009-1046-1 CrossRefPubMed

33.

Hubmacher D, Reinhardt DP, Plesec T, Schenke-Layland K, Apte SS (2014) Human eye development is characterized by coordinated expression of fibrillin isoforms. Invest Ophthalmol Vis Sci 55:7934–7944. https://doi.org/10.1167/iovs.14-15453 CrossRefPubMedPubMedCentral

34.

Inoue T, Ohbayashi T, Fujikawa Y, Yoshida H, Akama TO, Noda K et al (2014) Latent TGF-β binding protein-2 is essential for the development of ciliary zonule microfibrils. Hum Mol Genet 23:5672–5682. https://doi.org/10.1093/hmg/ddu283 CrossRefPubMedPubMedCentral

35.

Liu W, Qian C, Comeau K, Brenn T, Furthmayr H, Francke U (1996) Mutant fibrillin-1 monomers lacking EGF-like domains disrupt microfibril assembly and cause severe marfan syndrome. Hum Mol Genet 5:1581–1587CrossRefPubMed

36.

Vrhovski B, Jensen S, Weiss AS (1997) Coacervation characteristics of recombinant human tropoelastin. Eur J Biochem 250:92–98CrossRefPubMed

37.

Mithieux SM, Weiss AS (2005) Elastin. Adv Protein Chem 70:437–461. https://doi.org/10.1016/S0065-3233(05)70013-9 CrossRefPubMed

38.

Nakamura T, Lozano PR, Ikeda Y, Iwanaga Y, Hinek A, Minamisawa S et al (2002) Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 415:171–175. https://doi.org/10.1038/415171a CrossRefPubMed

39.

Nakamura T, Ruiz-Lozano P, Lindner V, Yabe D, Taniwaki M, Furukawa Y et al (1999) DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries. J Biol Chem 274:22476–22483CrossRefPubMed

40.

Yanagisawa H, Davis EC, Starcher BC, Ouchi T, Yanagisawa M, Richardson JA et al (2002) Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature 415:168–171. https://doi.org/10.1038/415168a CrossRefPubMed

41.

Hirai M, Ohbayashi T, Horiguchi M, Okawa K, Hagiwara A, Chien KR, Kita T, Nakamura T (2007) Fibulin-5/DANCE has an elastogenic organizer activity that is abrogated by proteolytic cleavage in vivo. J Cell Biol 176:1061–1071. https://doi.org/10.1083/jcb.200611026 CrossRefPubMedPubMedCentral

42.

Rifkin DB (2005) Latent transforming growth factor-beta (TGF-beta) binding proteins: orchestrators of TGF-beta availability. J Biol Chem 280:7409–7412. https://doi.org/10.1074/jbc.R400029200 CrossRefPubMed

43.

Todorovic V, Rifkin DB (2012) LTBPs, more than just an escort service. J Invest Dermatol 132:448–457. https://doi.org/10.1002/jcb.23385 CrossRefPubMed

44.

Saharinen J, Keski-Oja J (2000) Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates a hydrophobic interaction surface for binding of small latent TGF-beta. Mol Biol Cell 11:2691–2704CrossRefPubMedPubMedCentral

45.

Ali M, McKibbin M, Booth A, Parry DA, Jain P, Riazuddin SA et al (2009) Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet 84:664–671. https://doi.org/10.1016/j.ajhg.2009.03.017 CrossRefPubMedPubMedCentral

46.

Narooie-Nejad M, Paylakhi SH, Shojaee S, Fazlali Z, Rezaei Kanavi M, Nilforushan N et al (2009) Loss of function mutations in the gene encoding latent transforming growth factor beta binding protein 2, LTBP2, cause primary congenital glaucoma. Hum Mol Genet 18:3969–3977. https://doi.org/10.1093/hmg/ddp338 CrossRefPubMed

47.

Azmanov DN, Dimitrova S, Florez L, Cherninkova S, Draganov D, Morar B et al (2011) LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/gypsy founder population. Eur J Hum Genet 19:326–333. https://doi.org/10.1038/ejhg.2010.181 CrossRefPubMed

48.

Noda K, Dabovic B, Takagi K, Inoue T, Horiguchi M, Hirai M et al (2013) Latent TGF-β binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5. Proc Natl Acad Sci U S A 110:2852–2857. https://doi.org/10.1073/pnas.1215779110 CrossRefPubMedPubMedCentral

49.

Smith RS, John SWM, Nishina PM, Sundberg JP (2001) Systematic evaluation of the mouse eye: anatomy, pathology, and biomethods. CRC Press, Boca Raton, FL, pp 45–63CrossRef

50.

Kawamoto T, Kawamoto K (2014) Preparation of thin frozen sections from nonfixed and undecalcified hard tissues using Kawamot’s film method (2012). Methods Mol Biol 130:149–164. https://doi.org/10.1007/978-1-62703-989-5_11 CrossRef

51.

Yoshimura N (2016) Age-related macular degeneration. Nippon Ganka Gakkai Zasshi [in Japanese] 120:163–188

52.

Ho AC, Yannuzzi LA, Pisicano K, DeRosa J (1995) The natural history of idiopathic subfoveal choroidal neovascularization. Ophthalmology 102:782–789CrossRefPubMed

53.

Imamura Y, Engelbert M, Iida T, Freund KB, Yannuzzi LA (2010) Polypoidal choroidal vasculopathy: a review. Surv Ophthalmol 55:501–515. https://doi.org/10.1016/j.survophthal.2010.03.004 CrossRefPubMed

54.

Jalali S, Parra SL, Majji AB, Hussain N, Shah V (2006) Ultrasonographic charac-teristics and treatment outcomes of surgery for vitreous hemorrhage in idiopathic polypoidal choroidal vasculopathy. Am J Ophthalmol 142:608–619. https://doi.org/10.1016/j.ajo.2006.05.055 CrossRefPubMed

55.

Yannuzzi LA, Negrão S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J et al (2012) Retinal angiomatous proliferation in age-related macular degeneration. Retina 21:416–434CrossRef

56.

Nagai N, Lundh von Leithner P, Izumi-Nagai K, Hosking B, Chang B, Hurd R et al (2014) Spontaneous CNV in a novel mutant mouse is associated with early VEGF-A-driven angiogenesis and late-stage focal edema, neural cell loss, and dysfunction. Invest Ophthalmol Vis Sci 55:3709–3719. https://doi.org/10.1167/iovs.14-13989 CrossRefPubMedPubMedCentral

57.

Mullins RF, Olvera MA, Clark AF, Stone EM (2007) Fibulin-5 distribution in human eyes: relevance to age-related macular degeneration. Exp Eye Res 84:378–380. https://doi.org/10.1016/j.exer.2006.09.021 CrossRefPubMed

58.

Hogan MJ, Alvarado J (1967) Studies on the human macula. IV. Aging changes in Bruch’s membrane. Arch Ophthalmol 77:410–420CrossRefPubMed

59.

Sarks SH (1976) Ageing and degeneration in the macular region: a clinico-pathological study. Br J Ophthalmol l60:324–341CrossRef

60.

Green WR, McDonnell PJ, Yeo JH (1985) Pathologic features of senile macular degeneration. Ophthalmology 92:615–627CrossRefPubMed

61.

Grindle CF, Marshall J (1978) Ageing changes in Bruch’s membrane and their functional implications. Trans Ophthalmol Soc U K 98:172–175PubMed

62.

Feeney-Burns L, Ellersieck MR (1985) Age-related changes in the ultrastructure of Bruch’s membrane. Am J Ophthalmol 100:686–697CrossRefPubMed

63.

Ramrattan RS, van der Schaft TL, Mooy CM, de Bruijn WC, Mulder PG, de Jong PT (1994) Morphometric analysis of Bruch's membrane, the choriocapillaris, and the choroid in aging. Invest Ophthalmol Vis Sci 35:2857–2864PubMed

64.

Spraul CW, Lang GE, Grossniklaus HE, Lang GK (1999) Histologic and morphometric analysis of the choroid, Bruch’s membrane, and retinal pigment epithelium in postmortem eyes with age-related macular degeneration and histologic examination of surgically excised choroidal neovascular membranes. Surv Ophthalmol 44:S10–S32CrossRefPubMed

65.

Majji AB, Cao J, Chang KY, Hayashi A, Aggarwal S, Grebe RR et al (2000) Age-related retinal pigment epithelium and Bruch’s membrane degeneration in senescence-accelerated mouse. Invest Ophthalmol Vis Sci 41:3936–3942PubMed

66.

Schmidt-Erfurth U, Rudolf M, Funk M, Hofmann-Rummelt C, Franz-Haas NS, Aherrahrou Z et al (2008) Ultrastructural changes in a murine model of graded Bruch membrane lipoidal degeneration and corresponding VEGF164 detection. Invest Ophthalmol Vis Sci 49:390–398. https://doi.org/10.1167/IOVS.07-0227 CrossRefPubMed

67.

Sato R, Yasukawa T, Kacza J, Eichler W, Nishiwaki A, Iandiev I et al (2013) Three-dimensional spheroidal culture visualization of membranogenesis of Bruch’s membrane and basolateral functions of the retinal pigment epithelium. Invest Ophthalmol Vis Sci 54:1740–1749. https://doi.org/10.1167/iovs.12-10068 CrossRefPubMed

Title: Developmental and age-related changes to the elastic lamina of Bruch’s membrane in mice
Authors: Hidetsugu Mori
Haruhiko Yamada
Keiko Toyama
Kanji Takahashi
Tomoya Akama
Tadashi Inoue
Tomoyuki Nakamura
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 2/2019
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-018-4184-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Developmental and age-related changes to the elastic lamina of Bruch’s membrane in mice

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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