Skip to main content
SpringerLink
Log in

Corticosteroids and daunomycin in the prevention of experimental proliferative vitreoretionopathy induced by macrophages

  • Laboratory Investigations
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

An experimental model of proliferative vitreoretionpathy (PVR) induced by macrophages simulates a special form of wound healing process in the eye and mimics the development of PVR from its initial stage. We used this model for the evaluation of drug efficacy in the prevention of PVR. One mg triamcinolone acetonide (TA), 10 μg daunomycin-liposome (DL), 5 μg free daunomycin (FD) and 0.1 ml saline or empty liposomes (as controls) were injected into the vitreous in four groups of animals (30 or 40 rabbit eyes each) after macrophage injection. Retinal detachment developed in 77.5% of the control eyes on day 28, compared to 13.3% of the TA-treated eyes (P<0.01), to 33.3% of the eyes treated with DL (P<0.01), and 50% of the FD-treated eyes (P<0.05). TA cleared up from the vitreous within 35–63 days (average 45.5 days). The half-time of FD clearance was 145.5 min. Although DL declined rapidly during the first 2 days, there was an average of 0.64 μg/ ml daunomycin in the vitreous on day 14. Transmission electron microscopy showed that FD at a dosage of over 5 μg or DL over 20 μg was toxic to the retina and that up to 4 mg TA was nontoxic. These results suggest that steroids such as TA, given at the inflammatory stage, can effectively and savely prevent the development of PVR, and that encapsulation in liposomes of cytotoxic agents such as daunomycin can enhance drug efficacy and reduce toxicity. The time course of initiation and development of PVR is important in the selection of particular drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alberts DS, Bachur NR, Holtzman JL (1971) The pharmacokinetics of daunomycin in man. Clin Pharmacol Ther 12:96–104

    Google Scholar 

  2. Alghadyan AA, Peyman GA, Khoobehi B, Liu KR (1988) Liposome-bound cyclosporine: retinal toxicity after intravitreal injection. Int Ophthalmol 12:105–107

    Google Scholar 

  3. Alghadyan AA, Peyman GA, Khoobehi B, Milner S, Liu KR (1988) Liposome-bound cyclosporine: clearance after intravitreal injection. Int Ophthalmol 12:109–112

    Google Scholar 

  4. Barza M, Stuart M, Szoka F (1987) Effect of size and lipid composition on the pharmacokinetics of intravitreal liposomes. Invest Ophthalmol Vis Sci 28:893–900

    Google Scholar 

  5. Blumenkranz MS, Hartzer MK (1989) The mechanism of action of drugs for the treatment of vitreoretinal scarring. In: Ryan SJ (ed) Retina, CV Mosby, St Louis, 3:401–411

    Google Scholar 

  6. Broekhuyse RM, Rademakers AJJM, van Vugt AHM, Winkens HJ (1990) Autoimmune responsiveness to retinal IRBP, S-antigen and opsin in proliferative vitreoretinopathy. Exp Eye Res 50:197–202

    Google Scholar 

  7. Chandler DB, Rozakis G, de Juan E, Machemer R (1985) The effect of triamcinolone acetonide on a refined experimental model of proliferative vitreoretinopathy. Am J Ophthalmol 99:686–690

    Google Scholar 

  8. Chandler DB, Hida T, Sheta S, Proia AD, Machemer R (1987) Improvement in efficacy of corticosteroid therapy in an animal model of proliferative vitreoretinopathy by pretreatment. Graefe's Arch Clin Exp Ophthalmol 225:259–265

    Google Scholar 

  9. Gilbert C, Hiscott P, Unger W, Grierson I, McLeod D (1988) Inflammation and the formation of epiretinal membranes. Eye 2 (Suppl):s140-s156

    Google Scholar 

  10. Hackett SF, Singer JH, Leschey KH, Campochiaro PA (1991) Thrombin is a stimulator of retinal pigment epithelial cell proliferation. Exp Eye Res 53:95–100

    Google Scholar 

  11. Hatchell DL, McAdoo T, Sheta S, King RT, Bartolome JV (1988) Quantification of cellular proliferation in experimental proliferative vitreoretinopathy. Arch Ophthalmol 106:669–672

    Google Scholar 

  12. Heath TD, Lopez NG, Lewis GP, Stern WH (1987) Antiproliferative and anticontractile effects of liposome encapsulated fluoroorotate. Invest Ophthalmol Vis Sci 28:1365–1372

    Google Scholar 

  13. Hitchins CA, Grierson I, Hiscott PS (1985) The effects of injections of cultured fibroblasts into the rabbit vitreous. Graefe's Arch Clin Exp Ophthalmol 223:237–249

    Google Scholar 

  14. Hui YN, Goodnight R, Sorgente N, Ryan SJ (1989) Fibrovascular proliferation and retinal detachment after intravitreal injection of activated macrophages in the rabbit eye. Am J Ophthalmol 108:176–184

    Google Scholar 

  15. Hui YN, Sorgente N, Ryan SJ (1987) Posterior vitreous separation and retinal detachment induced by macrophages. Graefe's Arch Clin Exp Ophthalmol 225:279–284

    Google Scholar 

  16. Joondeph BC, Peyman GA, Khoobehi B, Yue BY (1988) Liposome-encapsulated 5-fluorouracil in the treatment of proliferative vitreoretinopathy. Ophthalmic Surg 19:252–256

    Google Scholar 

  17. Khawly JA, Saloupis P, Hatchell DL, Machemer R (1991) Daunorubicin treatment in a refined experimental model of proliferative vitreoretinopathy. Graefe's Arch Clin Exp Ophthalmol 229:464–467

    Google Scholar 

  18. Kirchhof B, Sorgente N (1989) Pathogenesis of proliferative vitreoretinopathy. Dev Ophthalmol 16:1–53

    Google Scholar 

  19. Lee VHL, Urrea PT, Smith RE, Schanzlin DJ (1985) Ocular drug bioavailablity from topically applied liposomes. Surv Ophthalmol 29:335–348

    Google Scholar 

  20. Lemor M, Yeo JH, Glaser BM (1986) Oral colchicine for the treatment of experimental traction retinal detachment. Arch Ophthahnol 104:1226–1229

    Google Scholar 

  21. Liu KR, Peyman GA, Khoobehi B, Alkan H, Fiscella R (1987) Intravitreal liposome-encapsulated trifluorothymidine in a rabbit model. Ophthalmology 94:1155–1159

    Google Scholar 

  22. Liu KR, Peyman GA, She SC, Niesman MR, Khoobehi B (1989) Reduced toxicity of intravitreally injected liposome-encapsulated cytarabine. Ophthalmic Surg 20:358–361

    Google Scholar 

  23. Machemer R (1988) Proliferative vitreoretinopathy: a personal account of its pathogenesis and treatment. Invest Ophthalmol Vis Sci 29:1771–1783

    Google Scholar 

  24. Peyman GA, Schulman J (1985) Proliferative vitreoretinopathy and chemotherapeutic agents. Surv Ophthalmol 29:434–442

    Google Scholar 

  25. Ryan SJ (1985) The pathophysiology of proliferative vitreoretinopathy in its management. Am J Ophthalmol 100:188–193

    Google Scholar 

  26. Santana M, Wiedemann P, Kirmani M, Minckler DS, Patterson R, Sorgente N, Ryan SJ (1984) Daunomycin in the treatment of experimental proliferative vitreoretinopathy: retinal toxicity of intravitreal daunomycin in the rabbit. Graefe's Arch Clin Exp Ophthalmol 221:210–213

    Google Scholar 

  27. Schindler RH, Chandler D, Thresher R, Machemer R (1982) The clearance of intravitreal triamcinolone acetonide. Am J Ophthalmol 93:415–417

    Google Scholar 

  28. Stern WH, Heath TD (1989) Drug delivery systems for treatment of proliferative vitreoretinopathy. In: Ryan SJ (ed) Retina, CV Mosby, St Louis, 3:413–417

    Google Scholar 

  29. Stern WH, Heath TD, Lewis GP, Guerin CJ, Erickson PA, Lopez NG, Hong K (1987) Clearance and localization of intravitreal liposomes in the aphakic vitrectomized eye. Invest Ophthalmol Vis Sci 28:907–911

    Google Scholar 

  30. Szoka F, Papahadjopoulos D (1978) Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci USA 75:4194–4198

    Google Scholar 

  31. Tano Y, Chandler D, Machemer R (1980) Treatment of intraocular proliferation with intravitreal injection of triamcinolone acetonide. Am J Ophthalmol 90:810–816

    Google Scholar 

  32. Tremblay C, Barza M, Szoka F, Lahav M, Baum J (1985) Reduced toxicity of liposome-associated amphotericin B injected intravitreally in rabbits. Invest Ophthalmol Vis Sci 26:711–718

    Google Scholar 

  33. Weller M, Wiedemann P, Heimann K (1990) Proliferative vitreoretinopathy — is it anything more than wound healing at the wrong place? Int Ophthalmol 14:105–117

    Google Scholar 

  34. Wiedemann P, Kirmani M, Santana M, Sorgente N, Ryan SJ (1983) Control of experimental massive periretinal proliferation by daunomycin: dose response relation. Graefe's Arch Clin Exp Ophthalmol 220:233–235

    Google Scholar 

  35. Wiedemann P, Sorgente N, Bekhor C, Patterson R, Tran T, Ryan SJ (1985) Daunomycin in the treatment of experimental proliferative vitreoretinopathy. Effective doses in vitro and in vivo. Invest Ophthalmol Vis Sci 26:719–725

    Google Scholar 

  36. Wiedemann P, Leinung C, Hilgers RD, Heimann K (1991) Daunomycin and silicone oil for the treatment of proliferative vitreoretinopathy. Graefe's Arch Clin Exp Ophthalmol 229:150–152

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Eye Center, Xijing Hospital, Fourth Military Medical University, 710032, Xian, Peoples Republic of China

    Yan-Nian Hui, Hou-Cheng Liang & Yong-Shu Cai

  2. Universitäts-Augenklinik, Joseph- Stelzmann-Straße 9, 5000, Köln 41, Germany

    Bernd Kirchhof & Klaus Heimann

Authors
  1. Yan-Nian Hui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hou-Cheng Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong-Shu Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernd Kirchhof
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Klaus Heimann
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by DAAD/K.C. Wong Fellowship

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hui, YN., Liang, HC., Cai, YS. et al. Corticosteroids and daunomycin in the prevention of experimental proliferative vitreoretionopathy induced by macrophages. Graefe's Arch Clin Exp Ophthalmol 231, 109–114 (1993). https://doi.org/10.1007/BF00920223

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00920223

Keywords

Search

Navigation