Fast in situ enzymatic gelation of PPO-PEO block copolymer for injectable intraocular lens in vivo

Abstract

Foldable intraocular lenses (IOLs) have been utilized to substitute natural lens of cataract patients. In this study, we developed a fast, in situ gelable hydrogel requiring no toxic agent as an injectable IOL material. A 4-armed PPO/PEO-phenol conjugate by a non-degradable linker was synthesized to form a hydrogel in situ by horseradish peroxidase. The gelation time and modulus could be controlled, ranging from 20 s to 2 min and from 1 to 43 kPa. The adhesion of human lens epithelial cells on the hydrogel was significantly reduced compared to that on commercial IOLs. The hydrogels were injected into the rabbit eyes to evaluate the in vivo biocompatibility for 8 weeks. Corneal endothelial cell loss and central corneal thickness were comparable with the common IOL implantation procedure. Histologically, the cornea and retina showed the intact structure. The change of refraction after application of pilocarpine was +0.42 D preoperatively and +0.83 D postoperatively, which may indicate the maintenance of accommodation amplitude.

Keywords

Injectable intraocular lens hydrogel enzymatic cross-linking PPO-PEO block copolymers

Get full access to this article

View all access options for this article.

References

Michael

Bron

. The ageing lens and cataract: a model of normal and pathological ageing. Philos Trans R Soc B Biol Sci 2011; 366: 1278–1292.

De Groot

Van Beijma

Haitjema

. Injectable intraocular lens materials based upon hydrogels. Biomacromolecules 2001; 2: 628–634.

Chehade

Elder

. Intraocular lens materials and styles. Aust N Z J Ophthalmol 1997; 25: 255–263.

Kohnen

. The variety of foldable intraocular lens materials. J Cataract Refract Surg 1996; 22: 1255–1258.

Parel

Gelender

Trefers

. Phaco-ersatz: cataract surgery designed to preserve accommodation. Graefes Arch Clin Exp 1986; 224: 165–173.

Kessler

. Experiments in refilling the lens. Arch Ophthalmol 1964; 71: 412–417.

Menapace

Findl

Kriechbaum

. Accommodating intraocular lenses: a critical review of present and future concepts. Graefes Arch Clin Exp 2007; 245: 473–489.

Gindi

Wan

Schanzlin

. Endocapsular cataract surgery. Cataract 1985; 2: 6–10.

Haefliger

Parel

Fantes

. Accommodation of an endocapsular silicone lens (phaco-ersatz) in the nonhuman primate. Ophthalmology 1987; 94: 471–477.

10.

Nishi

. Refilling the lens of the rabbit eye after intercapsular cataract surgery using an endocapsular balloon and an anterior capsule suturing technique. J Cataract Refract Surg 1989; 15: 450–454.

11.

Nishi

. Accommodation amplitude after lens refilling with injectable silicone by sealing the capsule with a plug in primates. Arch Ophthalmol 1998; 116: 1358–1361.

12.

Koopmans

Terwee

Glasser

. Accommodative lens refilling in rhesus monkeys. Invest Ophthalmol Vis Sci 2006; 47: 2976–2984.

13.

Nishi

. Capsular bag refilling using a new accommodating intraocular lens. J Cataract Refract Surg 2008; 34: 302–309.

14.

Hettlich

Lucke

Asiyo-Vogel

. Lens refilling and endocapsular polymerization of an injectable intraocular lens: in vitro and in vivo study of potential risks and benefits. J Cataract Refract Surg 1994; 20: 115–123.

15.

de Groot

Spaans

van Calck

. Hydrogels for an accommodating intraocular lens. An explorative study. Biomacromolecules 2003; 4: 608–616.

16.

Han

Kwon

Kim

. In vitro and in vivo study of lens refilling with poloxamer hydrogel. Br J Ophthalmol 2003; 87: 1399–1402.

17.

Kwon

Han

Lee

. Biocompatibility of poloxamer hydrogel as an injectable intraocular lens: a pilot study. J Cataract Refract Surg 2005; 31: 607–613.

18.

Yoo

Choi

Lee

. Injectable intraocular lens using hydrogels. J Drug Deliv Sci Technol 2007; 17: 81–85.

19.

Aliyar

Hamilton

Ravi

. Refilling of ocular lens capsule with copolymeric hydrogel containing reversible disulfide. Biomacromolecules 2005; 6: 204–211.

20.

Koopmans

Terwee

van Kooten

. Prevention of capsular opacification after accommodative lens refilling surgery in rabbits. Biomaterials 2011; 32: 5743–5755.

21.

Nishi

Mano

. Lens refilling with injectable silicone in rabbit eyes. J Cataract Refract Surg 1998; 24: 975–982.

22.

Jin

Hiemstra

Zhong

. Enzyme-mediated fast in situ formation of hydrogels from dextran-tyramine conjugates. Biomaterials 2007; 28: 2791–2800.

23.

Kurisawa

Chung

Yang

. Injectable biodegradable hydrogels composed of hyaluronic acid-tyramine conjugates for drug delivery and tissue engineering. Chem Commun 2005; 41(34): 4312–4314.

24.

Park

Shin

Joung

. In situ forming hydrogels based on tyramine conjugated 4-arm-ppo-peo via enzymatic oxidative reaction. Biomacromolecules 2010; 11: 706–712.

25.

Park

Jun

Joung

. In situ hydrogelation and rgd conjugation of tyramine-conjugated 4-arm ppo-peo block copolymer for injectable bio-mimetic scaffolds. Soft Matter 2011; 7: 986–992.

26.

Park

Lee

Son

. Synthesis and characterizations of in situ cross-linkable gelatin and 4-arm-ppo-peo hybrid hydrogels via enzymatic reaction for tissue regenerative medicine. Biomacromolecules 2012; 13: 604–611.

27.

Barany

. Simultaneous measurement of changing intraocular pressure and outflow. Invest Ophthalmol 1964; 3: 135–143.

28.

Han

Yang

Hyon

. Toxicity of voriconazole on corneal endothelial cells in an animal model. Br J Ophthalmol 2012; 96: 905–908.

29.

Arnao

Acosta

Del Rio

. A kinetic study on the suicide inactivation of peroxidase by hydrogen peroxide. Biochim Biophys Acta: Prot Struct Mol Enzymol 1990; 1041: 43–47.

30.

Baynton

Bewtra

Biswas

. Inactivation of horseradish peroxidase by phenol and hydrogen peroxide: a kinetic investigation. Biochim Biophys Acta: Prot Struct Mol Enzymol 1994; 1206: 272–278.

31.

Weeber

Eckert

Soergel

. Dynamic mechanical properties of human lenses. Exp Eye Res 2005; 80: 425–434.

32.

Fisher

. The elastic constants of the human lens. J Physiol (Lond) 1971; 212: 147–180.

33.

Bertelmann

Kojetinsky

. Posterior capsule opacification and anterior capsule opacification. Curr Opin Ophthalmol 2001; 12: 35–40.

34.

McDonnell

Stark

Green

. Posterior capsule opacification: a specular microscopic study. Ophthalmology 1984; 91: 853–856.

35.

Wormstone

. Posterior capsule opacification: A cell biological perspective. Exp Eye Res 2002; 74: 337–347.

36.

Emery

. Capsular opacification after cataract surgery and capsule. Curr Opin Ophthalmol 1998; 9: 60–65.

37.

Amon

Menapace

Papapanos

. Clinical results with three different pmma-iols for small incision cataract surgery. Spektrum Augenheilkd 1992; 6: 273–277.

38.

Yamanaka

Kazusa

Takayama

. Cells on the various kinds of intraocular lens implants. Eur J Imp Refract Surg 1989; 1: 15–17.

39.

Tehrani

Dick

Wolters

. Material properties of various intraocular lenses in an experimental study. Ophthalmologica 2004; 218: 57–63.

40.

Amon

Menapace

. In vivo documentation of cellular reactions on lens surfaces for assessing the biocompatibility of different intraocular implants. Eye 1994; 8: 649–656.

41.

Lin

Wang

Huang

. Modification of hydrophobic acrylic intraocular lens with poly(ethylene glycol) by atmospheric pressure glow discharge: a facile approach. Appl Surf Sci 2010; 256: 7354–7364.

42.

Abela-Formanek

Amon

Schauersberger

. Results of hydrophilic acrylic, hydrophobic acrylic, and silicone intraocular lenses in uveitic eyes with cataract: comparison to a control group. J Cataract Refract Surg 2002; 28: 1141–1152.

43.

Müllner-Eidenböck

Amon

Schauersberger

. Cellular reaction on the anterior surface of 4 types of intraocular lenses. J Cataract Refract Surg 2001; 27: 734–740.

44.

Mamalis

Edelhauser

Dawson

. Toxic anterior segment syndrome. J Cataract Refract Surg 2006; 32: 324–333.

45.

Awasthi

Guo

Wagner

. Posterior capsular opacification: a problem reduced but not yet eradicated. Arch Ophthalmol 2009; 127: 555–562.

46.

Hao

Jeffery

TPT

. High refractive index polysiloxane as injectable, in situ curable accommodating intraocular lens. Biomaterials 2012; 33: 5659–5671.

47.

Nishi

Mano

. Controlling the capsular shape in lens refilling. Arch Ophthalmol 1997; 115: 507–510.

48.

Mishima

. Clinical investigations on the corneal endothelium. Ophthalmology 1982; 89: 525–530.

49.

Anonymous. Long-term corneal endothelial cell loss after cataract surgery. Results of a randomized controlled trial. Arch Ophthalmol 1986; 104: 1170–1175.

50.

Lucena

Ribeiro

MSA

Messias

. Comparison of corneal changes after phacoemulsification using bss plus versus lactated ringer's irrigating solution: a prospective randomised trial. Br J Ophthalmol 2011; 95: 485–489.

51.

Kim

Wee

Lee

. The comparison between torsional and conventional mode phacoemulsification in moderate and hard cataracts. Korean J Ophthalmol 2010; 24: 336–340.

52.

Lerman

Borkman

. Spectroscopic evaluation and classification of the normal, aging, and cataractous lens. Ophthalmic Res 1976; 8: 335–353.